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Huang YX, Tang Q, Fu SH, Zhong HJ, Liu Z, Zhong QY, Wang YH, Luo YD, Li XY, Chen S, Zhu HP. Comparison of Efavirenz and Dolutegravir on Gut Microbiome and Gut Barrier Functions. ACS OMEGA 2025; 10:23099-23110. [PMID: 40521525 PMCID: PMC12163826 DOI: 10.1021/acsomega.5c01210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 05/14/2025] [Accepted: 05/22/2025] [Indexed: 06/18/2025]
Abstract
Dolutegravir (DTG) is increasingly replacing efavirenz (EFV) as the recommended first-line antiretroviral therapy (cART) component due to its superior tolerance. However, both EFV-based and DTG-based cART regimens are associated with metabolic and neuropsychiatric disorders through mechanisms that remain poorly understood. In this study, the abundance of Lactobacillus was significantly reduced, along with elevated soluble CD14 levels, in HIV-1-infected individuals receiving EFV-based cART compared to those on DTG-based cART. Additionally, EFV treatment in mice resulted in the destruction of intestinal crypts, loss of goblet cells, decreased expression of intestinal ZO-1, and more severe damage to gut barrier integrity compared to the DTG and normal control groups. Furthermore, we identified a significant reduction in Lactobacillus in EFV-treated mice. Our results suggest that EFV and DTG may directly lead to gut dysbiosis and compromised gut barrier integrity, which could be targeted to prevent the side effects associated with EFV and DTG.
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Affiliation(s)
- Yong-Xiang Huang
- Science
and Technology Innovation Center, Guangzhou
University of Chinese Medicine, No. 12 Jichang Road, Guangzhou510405, China
| | - Qin Tang
- Science
and Technology Innovation Center, Guangzhou
University of Chinese Medicine, No. 12 Jichang Road, Guangzhou510405, China
- Jiangxi
Provincial People’s Hospital & The First Affiliated Hospital
of Nanchang Medical College, No. 152 Ai-guo Road, Nanchang330006, China
| | - Shi-Hua Fu
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
| | - Hui-Jun Zhong
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
| | - Zhe Liu
- Science
and Technology Innovation Center, Guangzhou
University of Chinese Medicine, No. 12 Jichang Road, Guangzhou510405, China
| | - Qing-Yang Zhong
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
| | - Yan-Hao Wang
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
| | - Yin-di Luo
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
| | - Xue-Ying Li
- Science
and Technology Innovation Center, Guangzhou
University of Chinese Medicine, No. 12 Jichang Road, Guangzhou510405, China
| | - Song Chen
- Science
and Technology Innovation Center, Guangzhou
University of Chinese Medicine, No. 12 Jichang Road, Guangzhou510405, China
| | - Hai-Peng Zhu
- Dongguan
Ninth People’s hospital, No. 88 Sha-di-tang Road, Dongguan523001, China
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2
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Si Y, Ma W, Zhang Q, Zhang Y, An J, Zhang M, Fu Y, Yu Y, Zhang H, Fang Y, Zhang D. Investigating acupuncture therapy in depression: mechanisms of synaptic plasticity regulation. Neuroscience 2025; 579:284-301. [PMID: 40506009 DOI: 10.1016/j.neuroscience.2025.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 05/06/2025] [Accepted: 06/05/2025] [Indexed: 06/16/2025]
Abstract
Depression is a severe heterogeneous mental illness that is highly co-morbid with other mental and somatic disorders. It poses a significant healthcare burden on both individuals and society. Currently, the use of single-target antidepressants exhibits suboptimal efficacy with significant adverse effects. Acupuncture has been advocated as a practical and effective treatment for depression, due to its low adverse effects rate compared to antidepressant medication. Currently, several studies have shown that acupuncture treatment for depression primarily involves multiple therapeutic mechanisms, including the regulation of specific gene expression, neuropeptide and neurotransmitter release, increasing the expression of neurotrophic factors, suppressing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, attenuating inflammatory responses, and restoring gut microbiota balance. These therapeutic effects involve the regulation of critical signaling pathways, including the cAMP-responsive element binding protein (CREB) signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, mechanistic target of rapamycin (mTOR) signaling pathway, and toll-like receptors (TLR) signaling pathway. Notably, depression-associated molecular mechanisms and signaling pathway dysregulations are closely linked to impaired neural and synaptic plasticity. Acupuncture synergistically modulates the neuro-immune-microbiome multidimensional network and integrates crosstalk among key pathways such as CREB, thereby systemically restoring synaptic plasticity. This multi-dimensional integrative mechanism likely underlies its therapeutic superiority over single-target antidepressants. This review aims to elucidate how acupuncture restores cerebral synaptic plasticity by rectifying depression-related systemic dysfunctions and signaling pathway abnormalities, which will advance our understanding of its regulatory potential in depression treatment and inform the development of precision therapeutic strategies.
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Affiliation(s)
- Yuxin Si
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Weigang Ma
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Qingxiang Zhang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Youlin Zhang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Jiaying An
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Miao Zhang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yu Fu
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yujie Yu
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Han Zhang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yuxin Fang
- Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 301617, PR China; Tianjin Key Laboratory of Modern Chinese Medicine Theory of Innovation and Application, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; State Key Laboratory of Chinese Medicine Modernization, Tianjin 301617, PR China.
| | - Di Zhang
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Tianjin Key Laboratory of Intelligent and Green Pharmaceuticals for Traditional Chinese Medicine, Tianjin 301617, PR China; State Key Laboratory of Chinese Medicine Modernization, Tianjin 301617, PR China.
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3
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Amen RA, Hassan YM, Essmat RA, Ahmed RH, Azab MM, Shehata NR, Elgazzar MM, El-Sayed WM. Harnessing the Microbiome: CRISPR-Based Gene Editing and Antimicrobial Peptides in Combating Antibiotic Resistance and Cancer. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10573-8. [PMID: 40377870 DOI: 10.1007/s12602-025-10573-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2025] [Indexed: 05/18/2025]
Abstract
The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.
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Affiliation(s)
- Radwa A Amen
- Department of Biotechnology, Faculty of Science, Cairo University, Cairo, Egypt
| | - Yaser M Hassan
- Biotechnology Program, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt
| | - Rawan A Essmat
- Faculty of Pharmacy, Modern University for Information and Technology, Cairo, 11728, Egypt
| | - Rana H Ahmed
- Biotechnology Program, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
| | - Marwan M Azab
- Molecular Biotechnology Program, Faculty of Science, Helwan University, Ain Helwan, Cairo, Egypt
| | - Nadia R Shehata
- College of Biotechnology, Misr University for Science and Technology, Giza, 12596, Egypt
| | | | - Wael M El-Sayed
- Department of Zoology, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt.
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4
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Walczak ŁJ, Kosikowska U, Herbet M. The role and significance of the oncobiota in selected cancers: a review. Clin Exp Med 2025; 25:141. [PMID: 40335827 PMCID: PMC12058861 DOI: 10.1007/s10238-025-01598-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 02/10/2025] [Indexed: 05/09/2025]
Abstract
This review provides an overview of research evidence focused on the microbial components essential to clinical cancer care, called the oncobiota (the interaction of human microbiota and cancer cells). It specifically examines the oncobiota in central nervous system cancer,breast cancer, pancreatic cancer, liver cancer, lung cancer, and cervical cancer. The literature review reveals insufficient knowledge about the oncobiota of organs once considered sterile. Many studies on oncobiota focus on small, geographically specific patient groups, and the absence of a reference (control) group complicates the development of microbial profiles for selected cancers. Consequently, this review aims to analyze the literature data and reports on the role of oncobiota in selected "sterile" organs and the resulting therapeutic or preventive implications. All relevant publications on oncobiota in patients with the selected cancers were considered to provide the most thorough analysis possible. Understanding the significance and role of oncobiota in the pathomechanisms of carcinogenesis may pave the way for targeted cancer prevention methods. Furthermore, therapeutic strategies based on oncobiota could represent a novel area of personalized cancer treatment. Additionally, oncobiota may serve as an additional diagnostic tool in oncology.
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Affiliation(s)
- Łucja Justyna Walczak
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093, Lublin, Poland.
| | - Urszula Kosikowska
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093, Lublin, Poland.
| | - Mariola Herbet
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093, Lublin, Poland
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5
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Shi K, He Q, Zhao P, Li L, Liu Q, Wu Z, Wang Y, Dong H, Yu J. BGMDB: A curated database linking gut microbiota dysbiosis to brain disorders. Comput Struct Biotechnol J 2025; 27:879-886. [PMID: 40123802 PMCID: PMC11928979 DOI: 10.1016/j.csbj.2025.02.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 02/22/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
The gut microbiota is a fundamental component of human health and has been increasingly implicated in the etiology of neurological disorders. Neurotransmitters, acting as key mediators of gut-brain communication, are closely associated with both the progression and therapeutic modulation of brain diseases. Despite significant advancements in microbiome research, the complex interplay between gut microbiota and neurological disorders remains poorly understood, and a comprehensive resource integrating these associations is lacking. To bridge this gap, we developed the Brain Disease Gut Microbiota Database (BGMDB), a rigorously curated repository documenting experimentally validated relationships between gut microbiota and brain diseases. BGMDB encompasses 1419 associations involving 609 gut microbiota taxa and 43 brain disorders, along with 184 tripartite interactions linking brain diseases, neurotransmitters, and microbiota across six neurotransmitter systems. Additionally, BGMDB integrates genetic data from the gutMGene database, allowing users to explore microbiota-mediated genetic associations with brain disease pathology and neuroanatomical alterations. A user-friendly interface enables researchers to navigate relevant information through graphical query tools, comprehensive browsing functionalities, and data retrieval options. Our BGMDB provides an unparalleled resource for advancing mechanistic insights into gut-brain interactions, facilitating novel microbiota-targeted therapeutic strategies for neurological disorders. BGMDB is freely available at: http://bgmdb.online/bgmdb.
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Affiliation(s)
- Kai Shi
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
- Guangxi Key Laboratory of Embedded Technology and Intelligent Systems, Guilin University of Technology, Guilin, China
| | - Qisheng He
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | - Pengyang Zhao
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | - Lin Li
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | - Qiaohui Liu
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | - Zhengxia Wu
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | - Yanjun Wang
- College of Computer Science and Engineering, Guilin University of Technology, Guilin, China
| | | | - Juehua Yu
- International Research Center for Regenerative Medicine, BOAO International Hospital, Qionghai, China
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6
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Xu Q, Xiang Q, Tan Z, Yang Q. Global research trends in the intestinal microflora and depression: bibliometrics and visual analysis. Front Cell Infect Microbiol 2025; 15:1507667. [PMID: 40070374 PMCID: PMC11893873 DOI: 10.3389/fcimb.2025.1507667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/07/2025] [Indexed: 03/14/2025] Open
Abstract
Background In recent years, the relationship between gut microbiota and human health has garnered significant attention. Notably, the potential connection between gut microbiota and mental health issues, such as depression and anxiety, has emerged as a new focal point for research. While some studies suggest a possible link between these factors, the field remains in its early stages of development, and there are notable methodological and sample size limitations. Purpose This study aims to systematically summarize the knowledge systems, research hotspots, and development trends related to intestinal microflora within the context of depression research. Methods This study conducted a search for publications related to intestinal microflora and depression in the Web of Science Core Collection (WOSCC) prior to August 6, 2024. The selected literature was subsequently analyzed using VOSviewer (v.1.6.20), SCImago Graphica (v.1.0.39), and CiteSpace (v.6.3.1). Results The study encompassed a total of 1,046 publications, demonstrating a consistent increase in annual publication volume. The primary research countries identified are China and the United States, with notable contributions from institutions such as the University of California and University College Cork, among others. Keywords analysis highlighted high-frequency terms including "gut microbiota," "depression," and "anxiety," and revealed 10 keyword clusters along with 20 strongest citation bursts keywords. The focus of research has shifted from compositional analysis of gut microbiota to its role in the pathogenesis of depression. Conclusions Research on gut microbiota and depression is growing, but there is still a need for greater collaboration between authors and institutions across regions, more ongoing interaction and communication to further explore the mechanisms of action of gut microbiota, to develop microbiota-based interventions, and to facilitate translation of research findings into clinical practice.
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Affiliation(s)
- Qian Xu
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Qingwei Xiang
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Zihu Tan
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Qiong Yang
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
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7
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Dan Y, Xiong Y, Xu D, Wang Y, Yin M, Sun P, Ding Y, Feng Z, Sun P, Xia W, Yu G, Li L. Potential common targets of music therapy intervention in neuropsychiatric disorders: the prefrontal cortex-hippocampus -amygdala circuit (a review). Front Hum Neurosci 2025; 19:1471433. [PMID: 39963392 PMCID: PMC11832007 DOI: 10.3389/fnhum.2025.1471433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/17/2025] [Indexed: 02/20/2025] Open
Abstract
As life becomes more stressful, neurological disorders, psychiatric disorders, and comorbidities of the two are becoming more and more of a concern. Multiple neuropsychiatric disorders share the same mental and somatic dysfunction and may involve common brain circuits and mechanistic targets. Music therapy, as an art form with proven efficacy, low cost and few side effects, is promoted for use in interventions for neuropsychiatric disorders. This may be closely related to the release of signaling molecules such as monoamine neurotransmitters, the glutamatergic system, the gut-microbiota-brain axis, pro-inflammatory cytokines and the endogenous opioid peptide system. However, fewer studies have mentioned the main targets of music to promote functional changes in brain regions. Therefore, this paper is a review of the mechanisms by which music therapy interacts with the prefrontal cortex-hippocampus-amygdala circuit through the aforementioned molecules. It is also hypothesized that glial cells, mitochondria and microRNAs are microscopic targets for musical intervention in neuropsychiatric disorders. The aim is to give new ideas for future research into the biological mechanisms of music therapy intervention in neuropsychiatric disorders.
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Affiliation(s)
- Yuqin Dan
- The College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ying Xiong
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Danghan Xu
- Rehabilitation Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuqi Wang
- The College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Meng Yin
- Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, China
| | - Pengwei Sun
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yi Ding
- Department Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ziyun Feng
- Department Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Peng Sun
- Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Weili Xia
- Shandong Mental Health Center, Shandong University, Jinan, China
| | - Gongchang Yu
- Shandong Mental Health Center, Shandong University, Jinan, China
- Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Li Li
- The College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- Department Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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8
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Li C, Yuan Y, Jia Y, Zhou Q, Wang Q, Jiang X. Cellular senescence: from homeostasis to pathological implications and therapeutic strategies. Front Immunol 2025; 16:1534263. [PMID: 39963130 PMCID: PMC11830604 DOI: 10.3389/fimmu.2025.1534263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence and cancer is complex and multifaceted, senescence can both promote and inhibit tumor progression through various mechanisms. M6A methylation modification regulates the aging process of cells and tissues by modulating senescence-related genes. In this review, we comprehensively discuss the characteristics of cellular senescence, the signaling pathways regulating senescence, the biomarkers of senescence, and the mechanisms of anti-senescence drugs. Notably, this review also delves into the complex interactions between senescence and cancer, emphasizing the dual role of the senescent microenvironment in tumor initiation, progression, and treatment. Finally, we thoroughly explore the function and mechanism of m6A methylation modification in cellular senescence, revealing its critical role in regulating gene expression and maintaining cellular homeostasis. In conclusion, this review provides a comprehensive perspective on the molecular mechanisms and biological significance of cellular senescence and offers new insights for the development of anti-senescence strategies.
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Affiliation(s)
- Chunhong Li
- Department of Oncology, Suining Central Hospital, Suining, Sichuan, China
| | - Yixiao Yuan
- Department of Medicine, Health Cancer Center, University of Florida, Gainesville, FL, United States
| | - YingDong Jia
- Gastrointestinal Surgical Unit, Suining Central Hospital, Suining, Sichuan, China
| | - Qiang Zhou
- Department of Oncology, Suining Central Hospital, Suining, Sichuan, China
| | - Qiang Wang
- Gastrointestinal Surgical Unit, Suining Central Hospital, Suining, Sichuan, China
| | - Xiulin Jiang
- Department of Medicine, Health Cancer Center, University of Florida, Gainesville, FL, United States
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9
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Rodiño-Janeiro BK, Khannous-Lleiffe O, Pigrau M, Willis JR, Salvo-Romero E, Nieto A, Expósito E, Fortea M, Pardo-Camacho C, Albert-Bayo M, González-Castro AM, Guagnozzi D, Martínez C, Lobo B, Vicario M, Santos J, Gabaldón T, Alonso-Cotoner C. Acute stress triggers sex-dependent rapid alterations in the human small intestine microbiota composition. Front Microbiol 2025; 15:1441126. [PMID: 39881982 PMCID: PMC11778178 DOI: 10.3389/fmicb.2024.1441126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 12/16/2024] [Indexed: 01/31/2025] Open
Abstract
Background/aims Digestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction. Methods Jejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined. Results Cold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes. Conclusions Acute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.
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Affiliation(s)
- Bruno K. Rodiño-Janeiro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Olfat Khannous-Lleiffe
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Marc Pigrau
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Jesse R. Willis
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Eloísa Salvo-Romero
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Adoración Nieto
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Elba Expósito
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Marina Fortea
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Cristina Pardo-Camacho
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Mercé Albert-Bayo
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Ana María González-Castro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Danila Guagnozzi
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Martínez
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Renal Physiopathology Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Beatriz Lobo
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - María Vicario
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Javier Santos
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Toni Gabaldón
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Carmen Alonso-Cotoner
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
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10
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Feng J, Cen Q, Cui Y, Hu X, Li M, Wang L, Wei J, Sun N, Wang J, Zhang A. Lactobacillus rhamnosus: An emerging probiotic with therapeutic potential for depression. Pharmacol Res 2025; 211:107541. [PMID: 39653301 DOI: 10.1016/j.phrs.2024.107541] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/18/2024] [Accepted: 12/06/2024] [Indexed: 12/16/2024]
Abstract
Depression, a complex psychological disorder, involves multiple biological pathways in its pathogenesis. In recent years, the gut-brain axis theory has provided novel insights into the pathogenesis of depression, particularly the crucial role of the gut microbiota in mood regulation. While there remains no universal consensus on the most efficacious strains for depression treatment, Lactobacillus rhamnosus has risen to prominence within the realm of probiotics for its potential to positively modulate depressive symptoms. This review preliminarily explores the clinical significance of Lactobacillus rhamnosus in the treatment of depression and summarizes the potential mechanisms by which Lactobacillus rhamnosus treats depression, including its regulation of gut microbiota, alterations in gene expression, improvement of intestinal barrier function, maintenance of neurotransmitter balance, suppression of inflammatory responses, modulation of the immune system, coping with oxidative stress, and optimization of metabolic processes. Future research needs to further explore these mechanisms and combine them with clinical research results to optimize treatment plans and provide more effective treatment options for patients with depression.
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Affiliation(s)
- Jing Feng
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Qiuyu Cen
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yanru Cui
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaomin Hu
- Department of Rehabilitation Medicine, General Hospital of Western Theater Command, Chengdu, China
| | - Min Li
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Linjie Wang
- Department of Rehabilitation Medicine, General Hospital of Western Theater Command, Chengdu, China
| | - Juanfang Wei
- College of Physical Education and Health, Geely University of China, Chengdu, China
| | - Nianyi Sun
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Junyu Wang
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Anren Zhang
- Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
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11
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Varghese SM, Patel S, Nandan A, Jose A, Ghosh S, Sah RK, Menon B, K V A, Chakravarty S. Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives. Mol Neurobiol 2024; 61:10398-10447. [PMID: 38730081 DOI: 10.1007/s12035-024-04205-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 04/19/2024] [Indexed: 05/12/2024]
Abstract
Depression is a highly prevalent psychological disorder characterized by persistent dysphoria, psychomotor retardation, insomnia, anhedonia, suicidal ideation, and a remarkable decrease in overall well-being. Despite the prevalence of accessible antidepressant therapies, many individuals do not achieve substantial improvement. Understanding the multifactorial pathophysiology and the heterogeneous nature of the disorder could lead the way toward better outcomes. Recent findings have elucidated the substantial impact of compromised blood-brain barrier (BBB) integrity on the manifestation of depression. BBB functions as an indispensable defense mechanism, tightly overseeing the transport of molecules from the periphery to preserve the integrity of the brain parenchyma. The dysfunction of the BBB has been implicated in a multitude of neurological disorders, and its disruption and consequent brain alterations could potentially serve as important factors in the pathogenesis and progression of depression. In this review, we extensively examine the pathophysiological relevance of the BBB and delve into the specific modifications of its components that underlie the complexities of depression. A particular focus has been placed on examining the effects of peripheral inflammation on the BBB in depression and elucidating the intricate interactions between the gut, BBB, and brain. Furthermore, this review encompasses significant updates on the assessment of BBB integrity and permeability, providing a comprehensive overview of the topic. Finally, we outline the therapeutic relevance and strategies based on BBB in depression, including COVID-19-associated BBB disruption and neuropsychiatric implications. Understanding the comprehensive pathogenic cascade of depression is crucial for shaping the trajectory of future research endeavors.
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Affiliation(s)
- Shamili Mariya Varghese
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Shashikant Patel
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Amritasree Nandan
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Anju Jose
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Soumya Ghosh
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Ranjay Kumar Sah
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Bindu Menon
- Department of Psychiatry, Amrita School of Medicine, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India
| | - Athira K V
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682 041, India.
| | - Sumana Chakravarty
- Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, Telangana, 500007, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
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12
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Ogulur I, Pat Y, Yazici D, Ardicli S, Ardicli O, Mitamura Y, Akdis M, Akdis CA. Epithelial barrier dysfunction, type 2 immune response, and the development of chronic inflammatory diseases. Curr Opin Immunol 2024; 91:102493. [PMID: 39321494 DOI: 10.1016/j.coi.2024.102493] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 09/07/2024] [Accepted: 09/11/2024] [Indexed: 09/27/2024]
Abstract
The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, humans have been increasingly exposed to substances toxic for epithelial cells, including air pollutants, laundry and dishwashers, household chemicals, toothpaste, food additives, microplastics, and nanoparticles, introduced into our daily lives as part of industrialization, urbanization, and modernization. These substances disrupt the epithelial barriers and lead to microbial dysbiosis and cause immune response to allergens, opportunistic pathogens, bacterial toxins, and autoantigens followed by chronic inflammation due to epigenetic mechanisms. Recent evidence from studies on the mechanisms of epithelial barrier damage has demonstrated that even trace amounts of toxic substances can damage epithelial barriers and induce tissue inflammation. Further research in this field is essential for our understanding of the causal substances and molecular mechanisms involved in the initiation of leaky epithelial barriers that cascade into chronic inflammatory diseases.
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Affiliation(s)
- Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
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13
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Jia W, Ma Q, Xing R, Yang X, Liu D, Zeng H, Liu Z, Liu S, Xu W, Liu Z, Wu W. Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines. Food Res Int 2024; 198:115306. [PMID: 39643357 DOI: 10.1016/j.foodres.2024.115306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 10/14/2024] [Accepted: 10/31/2024] [Indexed: 12/09/2024]
Abstract
Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics. JH was found to significantly alleviate CUMS-induced depression-like behavior by improving body weight, food intake, 1% sucrose preference, immobility time, and numbers of crossings and standings compared to Zhuyeqi black tea (ZYQ), which contains theaflavins. JH notably altered the gut microbiota composition, enriching genera such as Turicibacter, Faecalibaculum, Akkermansia, and Desulfovibrio, while inhibiting genera norank_f__Muribaculaceae and Lactobacillus. Additionally, JH modified the fecal metabolite profile, characterized by increased levels of several secondary bile acids (BAs) and decreased levels of several purine intermediate metabolites. Furthermore, JH upregulated levels of monoamine neurotransmitters (5-HT and DA) and brain-derived neurotrophic factor (BDNF), while downregulating pro-inflammatory cytokines IL-6 and TNF-α in brain tissue. These findings suggested that JH could mitigate CUMS-induced depression-like behavior, potentially by modulating gut microbiota composition and function, as well as brain neurochemicals and cytokines.
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Affiliation(s)
- Wenbao Jia
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China; Horticulture Colleges, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Qianting Ma
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China; Longping Branch, College of Biology, Hunan University, Changsha, Hunan 410125, China
| | - Ruixue Xing
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China; Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, China
| | - Xiaolu Yang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, China
| | - Dongmin Liu
- Changsha University of Science & Technology, Changsha 410114, China
| | - Hongliang Zeng
- Center of Medical Laboratory Animal, Hunan Academy of Chinese Medicine, Changsha, Hunan 410013, China
| | - Zhen Liu
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China
| | - Shujuan Liu
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China
| | - Wei Xu
- Horticulture Colleges, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, China.
| | - Wenliang Wu
- Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China; Longping Branch, College of Biology, Hunan University, Changsha, Hunan 410125, China.
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14
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Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X, Li M, Zhu X, Babayev H, Ardicli S, Ardicli O, D'Avino P, Kiykim A, Sokolowska M, van de Veen W, Weidmann L, Akdis D, Ozdemir BG, Brüggen MC, Biedermann L, Straumann A, Kreienbühl A, Guttman-Yassky E, Santos AF, Del Giacco S, Traidl-Hoffmann C, Jackson DJ, Wang DY, Lauerma A, Breiteneder H, Zhang L, O'Mahony L, Pfaar O, O'Hehir R, Eiwegger T, Fokkens WJ, Cabanillas B, Ozdemir C, Kistler W, Bayik M, Nadeau KC, Torres MJ, Akdis M, Jutel M, Agache I, Akdis CA. The epithelial barrier theory and its associated diseases. Allergy 2024; 79:3192-3237. [PMID: 39370939 DOI: 10.1111/all.16318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 10/08/2024]
Abstract
The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.
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Affiliation(s)
- Na Sun
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, P. R. China
| | - Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xiangting Bu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xueyi Zhu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Genetics, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Division of Food Processing, Milk and Dairy Products Technology Program, Karacabey Vocational School, Bursa Uludag University, Bursa, Turkey
| | - Paolo D'Avino
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ayca Kiykim
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Lukas Weidmann
- Department of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Deniz Akdis
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Marie Charlotte Brüggen
- Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Andrea Kreienbühl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Emma Guttman-Yassky
- Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | | | - David J Jackson
- Guy's Severe Asthma Centre, Guy's Hospital, Guy's & St Thomas' NHS Trust, London, UK
- School of Immunology & Microbial Sciences, King's College London, London, UK
| | - De-Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore City, Singapore
| | - Antti Lauerma
- Department of Dermatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Liam O'Mahony
- Department of Medicine and School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
| | - Robyn O'Hehir
- Allergy, Asthma & Clinical Immunology, The Alfred Hospital, Melbourne, Victoria, Australia
- Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Thomas Eiwegger
- Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria
| | - Wytske J Fokkens
- Department of Otorhinolaryngology & Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Beatriz Cabanillas
- Department of Allergy, Instituto de Investigación Biosanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Cevdet Ozdemir
- Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Turkey
- Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey
| | - Walter Kistler
- Department of Sports Medicine, Davos Hospital, Davos, Switzerland
- Swiss Research Institute for Sports Medicine (SRISM), Davos, Switzerland
- Medical Committee International Ice Hockey Federation (IIHF), Zurich, Switzerland
| | - Mahmut Bayik
- Department of Internal Medicine and Hematology, Marmara University, Istanbul, Turkey
| | - Kari C Nadeau
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Maria J Torres
- Allergy Unit, IBIMA-Hospital Regional Universitario de Málaga-ARADyAL, UMA, Málaga, Spain
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Marek Jutel
- Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland
| | - Ioana Agache
- Faculty of Medicine, Department of Allergy and Clinical Immunology, Transylvania University, Brasov, Romania
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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15
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Lu Y, Yu X, Wang Z, Kong L, Jiang Z, Shang R, Zhong X, Lv S, Zhang G, Gao H, Yang N. Microbiota-gut-brain axis: Natural antidepressants molecular mechanism. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 134:156012. [PMID: 39260135 DOI: 10.1016/j.phymed.2024.156012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUND Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis. PURPOSE This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain. METHODS To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action. RESULTS NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis. CONCLUSIONS NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.
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Affiliation(s)
- Yitong Lu
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Xiaowen Yu
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Department of Neurology, Affiliated Hospital of shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Zhongling Wang
- Department of Neurology, Affiliated Hospital of shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Linghui Kong
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Zhenyuan Jiang
- Department of Neurology, Affiliated Hospital of shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Ruirui Shang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Xia Zhong
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing 100191, China
| | - Shimeng Lv
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Guangheng Zhang
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Haonan Gao
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Ni Yang
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China
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Do NM. From Leaky Gut to Leaky Skin: A Clinical Review of Lifestyle Influences on the Microbiome. Am J Lifestyle Med 2024:15598276241292605. [PMID: 39540169 PMCID: PMC11556587 DOI: 10.1177/15598276241292605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
The microbiome connects the gut health to the rest of the body's organs, including the skin. The pathophysiology of intestinal dysbiosis leads to the expression "leaky gut." Ongoing speculations are aimed at restoring the gut microbiota via modulating lifestyle habits to prevent and potentially reverse autoimmunity. This review finds the connections between gut dysbiosis and skin conditions. It also collects evidence of some lifestyle pillars that influence the gut microbiome including dietary intakes, exercise, sleep, stress, and toxin exposures. It addresses why maintaining a healthy intestinal microbiome is important for the health of all organs in the human host. More people are affected by gut dysbiosis resulting in pro-inflammatory effects on different organs, like the cutaneous tissue, one of the largest epithelial surfaces. It is essential to take care of the gut health because this is where most of the immune system resides. The connection between the intestinal tract with its microbiota and the cutaneous system with its microbiota seems to be mediated by the immune system of the human host. Therefore, this review enhances the understanding of the research on the gut microbiome, its relationship to skin health, and the interplay between the gut and various autoimmune cutaneous conditions.
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Affiliation(s)
- Nhi Ma Do
- Arizona School of Health Sciences, A.T. Still University, Ormond Beach, FL, USA (NMD)
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Dong Z, Han K, Xie Q, Lin C, Shen X, Hao Y, Li J, Xu H, He L, Yu T, Kuang W. Core antibiotic resistance genes mediate gut microbiota to intervene in the treatment of major depressive disorder. J Affect Disord 2024; 363:507-519. [PMID: 39033825 DOI: 10.1016/j.jad.2024.07.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 06/20/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024]
Abstract
INTRODUCTION The relationship between depression and gut microbiota remains unclear, but an important role of gut microbiota has been verified. The relationship between gut microbiota and antibiotic resistance genes (ARGs) may be a potential new explanatory pathway. METHODS We collected samples from 63 depressed patients and 30 healthy controls for metagenomic sequencing. The two groups' microbiota characteristics, functional characteristics, and ARG differences were analyzed. RESULTS We obtained 30 differential KEGG orthologs (KOs) and their producers in 5 genera and 7 species by HUMAnN3. We found 6 KOs from Weissella_cibaria and Lactobacillus_plantaru are potentially coring functional mechanism of gut microbiota. Different metabolites including sphingolipids, pyrans, prenol lipids, and isoflavonoids also showed significance between MDD and HC. We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs, which indicated different mechanisms in affecting MDD. LIMITATIONS The present study needs to be replicated in different ethnic groups. At the same time, a larger Chinese cohort study and detailed experimental verification are also the key to further discussion. CONCLUSION Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota.
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Affiliation(s)
- Zaiquan Dong
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China; Department of Psychiatry, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Ke Han
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China; Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China
| | - Qinglian Xie
- Department of outpatient, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Chunting Lin
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, PR China
| | - Xiaoling Shen
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Yanni Hao
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Jin Li
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Haizhen Xu
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Lin He
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China; Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China
| | - Tao Yu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China; Shanghai Center for Women and Children's Health, 339 Luding Road, Shanghai 200062, PR China
| | - Weihong Kuang
- Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, PR China; Department of Psychiatry, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, PR China.
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18
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Duan DM, Wang YC, Hu X, Wang YB, Wang YQ, Hu Y, Zhou XJ, Dong XZ. Effects of regulating gut microbiota by electroacupuncture in the chronic unpredictable mild stress rat model. Neuroscience 2024; 557:24-36. [PMID: 39128700 DOI: 10.1016/j.neuroscience.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 07/04/2024] [Accepted: 08/06/2024] [Indexed: 08/13/2024]
Abstract
OBJECTIVE This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. METHODS A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. RESULTS In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. CONCLUSION This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.
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Affiliation(s)
- Dong-Mei Duan
- No.1 Health Care Department, Second Medical Center of Chinese, PLA General Hospital, 100853, China
| | - Yi-Chen Wang
- Chinese PLA Medical School, 100853, China; Chinese PLA General Hospital, 100853, China
| | - Xin Hu
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100853, China; School of Pharmacy, Zunyi Medical University, Zunyi 563000, China
| | - Yuan-Bo Wang
- Chinese PLA Medical School, 100853, China; Chinese PLA General Hospital, 100853, China
| | - Yu-Qing Wang
- Chinese PLA Medical School, 100853, China; Chinese PLA General Hospital, 100853, China
| | - Yuan Hu
- Chinese PLA General Hospital, 100853, China
| | | | - Xian-Zhe Dong
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100853, China.
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19
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Yue Y, Ke Y, Zheng J, Wang Z, Liu H, Liu S. Microbiota-derived tryptophan metabolism and AMPK/mTOR pathway mediate antidepressant-like effect of Shugan Hewei Decoction. Front Pharmacol 2024; 15:1466336. [PMID: 39351096 PMCID: PMC11439769 DOI: 10.3389/fphar.2024.1466336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 08/30/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction Depression is a common psychological disorder, accompanied by a disturbance of the gut microbiota and its metabolites. Recently, microbiota-derived tryptophan metabolism and AMPK/mTOR pathway were found to be strongly linked to the development of depression. Shugan Hewei Decoction (SHD) is a classical anti-depression traditional Chinese medicine formula. Although, we have shown that SHD exerted antidepressant effects via cecal microbiota and cecum NLRP3 inflammasome, the specific mechanism of SHD on metabolism driven by gut microbiota is unknown. In this study, we focus on the tryptophan metabolism and AMPK/mTOR pathway to elucidate the multifaceted mechanisms of SHD. Methods Male rats were established to the chronic unpredictable stress (CUS)/social isolation for 6 weeks, and SHD-L (7.34 g/kg/d), SHD-H (14.68 g/kg/d), Fructooligosaccharide (FOS) (3.15 g/kg/d) were given by intragastric administration once daily during the last 2 weeks. Behavioral experiments were carried out to evaluate the model. The colonic content was taken out for shotgun metagenomic sequencing combined with the untargeted metabolomics, the targeted tryptophan metabolomics. ELISA was used to detect the levels of zonula occludens 1 (ZO-1), Occludin in colon, as well as lipopolysaccharide (LPS), diamine oxidase (DAO), D-lactate (DLA) in serum. The expressions of mRNA and proteins of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway of autophagy were examined using RT-qPCR and Western blot in colon. Results SHD modulated gut microbiota function and biological pathways, which were related to tryptophan metabolism. In addition, SHD could regulate microbiota-derived tryptophan production (such as reduction of 3-HK, 3-HAA etc., increment of ILA, IAA etc.), which metabolites belong to kynurenine (KYN) and indole derivatives. Further, SHD reduced intestinal permeability and enhanced the intestinal barrier function. Moreover, SHD could upregulate the levels of AMPK, microtubule associated protein light chain 3 (LC3), autophagy related protein 5 (ATG5) and Beclin1, downregulate the levels of mTOR, p62, promoted autophagy in colon. Spearman's analysis illustrated the close correlation between tryptophan metabolites and intestinal barrier, AMPK/mTOR pathway. Conclusion SHD may exert antidepressant-like effects by regulating microbiota-derived tryptophan metabolism, and triggering the AMPK/mTOR pathway of autophagy, enhancing the intestinal barrier function.
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Affiliation(s)
- Yingying Yue
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
| | - Youlan Ke
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
| | - Junping Zheng
- Hubei Shizhen Laboratory, Wuhan, China
- School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, China
| | - Zicheng Wang
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
| | - Hongtao Liu
- Hubei Shizhen Laboratory, Wuhan, China
- School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, China
| | - Songlin Liu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
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20
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Liu M, Yan R, Lu S, Zhang P, Xu S. Pathogenesis and therapeutic strategies for cancer-related depression. Am J Cancer Res 2024; 14:4197-4217. [PMID: 39417166 PMCID: PMC11477823 DOI: 10.62347/wvvg5364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/29/2024] [Indexed: 10/19/2024] Open
Abstract
Depression is a common co-morbidity among cancer cases, which has a detrimental influence on cancer treatment and prognosis. Recent advancements in the neurobiology of depression and cancer pathophysiology have revealed several shared biobehavioral mechanisms and introduced new therapeutic strategies. In this review, we summarize the biological mechanisms driving cancer-related depression, including psychosocial factors, immuno-inflammatory processes, chronic stress, dysbiosis of gut microbiota, and medically-induced factors. Interventions used for cancer-related depression may include psychosocial therapies, pharmacological therapies, immunotherapies, psychobiological medications, and dietary strategies. This review could inspire the elucidation of possible co-occurring mechanisms and complex interactions between cancer and depression, provide an opportunity to propose faster and more effective therapies for cancer-related depression, and well as new strategies for cancer in the future.
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Affiliation(s)
- Meishan Liu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Ran Yan
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Shaoteng Lu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
| | - Ping Zhang
- Department of Neurology, Naval Medical Center of PLA, Naval Medical UniversityShanghai 200052, China
| | - Sheng Xu
- National Key Laboratory of Immunity and Inflammation and Institute of Immunology, Navy Medical University/Second Military Medical UniversityShanghai 200433, China
- Shanghai Institute of Stem Cell Research and Clinical TranslationShanghai 200120, China
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21
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Zhang L, Yin J, Sun H, Dong W, Liu Z, Yang J, Liu Y. The relationship between body roundness index and depression: A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. J Affect Disord 2024; 361:17-23. [PMID: 38815765 DOI: 10.1016/j.jad.2024.05.153] [Citation(s) in RCA: 31] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 05/26/2024] [Accepted: 05/28/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND Depression is linked to obesity. The body roundness index (BRI) provides a more accurate assessment of body and visceral fat levels than the body mass index or waist circumference. However, the association between BRI and depression is unclear. Therefore, we investigated this relationship using the National Health and Nutrition Examination Survey (NHANES) database. METHODS In this population-based cross-sectional study, data from 18,654 adults aged ≥20 years from the NHANES 2011-2018 were analyzed. Covariates, including age, gender, race/ethnicity, education level, marital status, poverty-income ratio, alcohol status, smoking status, hypertension, diabetes mellitus, cardiovascular disease, energy intake, physical activity, total cholesterol, and triglycerides were adjusted in multivariable logistic regression models. In addition, smooth curve fitting, subgroup analysis, and interaction testing were conducted. RESULTS After adjusting for covariates, BRI was positively correlated with depression. For each one-unit increase in BRI, the prevalence of depression increased by 8 % (odds ratio = 1.08, 95 % confidence interval = 1.05-1.10, P < 0.001). LIMITATIONS As this was a cross-sectional study, we could not determine a causal relationship between BRI and depression. Patients with depression in this study were not clinically diagnosed with major depressive disorder. CONCLUSION BRI levels were positively related to an increased prevalence of depression in American adults. BRI may serve as a simple anthropometric index to predict depression.
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Affiliation(s)
- Lu Zhang
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jiahui Yin
- College of Traditional Chinese Medicine, Shandong University of Chinese Medicine, Jinan, China
| | - Haiyang Sun
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenliang Dong
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zihui Liu
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jiguo Yang
- College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Yuanxiang Liu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
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Zhang Y, Lin Y, Xiong Y, Huang J, Liu Z. An Analysis of the Intestinal Microbiome Combined with Metabolomics to Explore the Mechanism of How Jasmine Tea Improves Depression in CUMS-Treated Rats. Foods 2024; 13:2636. [PMID: 39200564 PMCID: PMC11353544 DOI: 10.3390/foods13162636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/25/2024] [Accepted: 08/16/2024] [Indexed: 09/02/2024] Open
Abstract
Recently, research has confirmed that jasmine tea may help improve the depressive symptoms that are associated with psychiatric disorders. Our team previously found that jasmine tea improved the depressive-like behavior that is induced by chronic unpredictable mild stress (CUMS) in Sprague Dawley (SD) rats. We hypothesized that the metabolic disorder component of depression may be related to the gut microbiota, which may be reflected in the metabolome in plasma. The influence of jasmine tea on gut microbiota composition and the association with depressive-related indexes were explored. Furthermore, the metabolites in plasma that are related to the gut microbiota were identified. SD rats were treated with control or CUMS and administrated jasmine tea for 8 weeks. The 16S rRNA gene amplicon sequencing was used to analyze the gut microbiota in feces samples, and untargeted metabolomics was used to analyze the metabolites in plasma. The results found that jasmine tea significantly ameliorated the depressive behavior induced by CUMS, significantly improved the neurotransmitter concentration (BDNF and 5-HT), and decreased the pro-inflammation levels (TNF-α and NF-κB). The intervention of jasmine tea also alleviated the dysbiosis caused by CUMS; increased the relative abundance of Bacteroides, Blautia, Clostridium, and Lactobacillus; and decreased Ruminococcus and Butyrivibrio in the CUMS-treated rats. Furthermore, the serum metabolites of the CUMS-treated rats were reversed after the jasmine tea intervention, i.e., 22 were up-regulated and 18 were down-regulated, which may have a close relationship with glycerophospholipid metabolism pathways, glycine serine and threonine metabolism pathways, and nicotinate and nicotinamide metabolism pathways. Finally, there were 30 genera of gut microbiota related to the depressive-related indexes, and 30 metabolites in the plasma had a strong predictive ability for depressive behavior. Potentially, our research implies that the intervention of jasmine tea can ameliorate the depression induced by CUMS via controlling the gut flora and the host's metabolism, which is an innovative approach for the prevention and management of depression.
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Affiliation(s)
- Yangbo Zhang
- School of Pharmacy, Shaoyang University, Shaoyang 422000, China;
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; (Y.L.); (Y.X.); (J.H.)
| | - Yong Lin
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; (Y.L.); (Y.X.); (J.H.)
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China
| | - Yifan Xiong
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; (Y.L.); (Y.X.); (J.H.)
| | - Jianan Huang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; (Y.L.); (Y.X.); (J.H.)
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China
- Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; (Y.L.); (Y.X.); (J.H.)
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China
- Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China
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Wu S, Yuan G, Wu L, Zou L, Wu F. Identifying the association between depression and constipation: An observational study and Mendelian randomization analysis. J Affect Disord 2024; 359:394-402. [PMID: 38806066 DOI: 10.1016/j.jad.2024.05.124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Both depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. METHODS We first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). RESULTS About 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530-2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538-3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242-1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LIMITATION The exact mechanism by which depression affects constipation is still unclear. CONCLUSION This study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression.
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Affiliation(s)
- Shasha Wu
- Department of Gastroenterology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, PR China
| | - Guojun Yuan
- Department of Gastroenterology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, PR China
| | - Linlin Wu
- Department of Psychosomatic diseases, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, PR China
| | - Long Zou
- Department of Gastroenterology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, PR China.
| | - Feixiang Wu
- Department of Urology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, PR China.
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Xiao S, Yang Z, Yan H, Chen G, Zhong S, Chen P, Zhong H, Yang H, Jia Y, Yin Z, Gong J, Huang L, Wang Y. Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder. Transl Psychiatry 2024; 14:292. [PMID: 39013880 PMCID: PMC11253007 DOI: 10.1038/s41398-024-03012-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/27/2024] [Accepted: 07/04/2024] [Indexed: 07/18/2024] Open
Abstract
Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.
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Affiliation(s)
- Shu Xiao
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Zibin Yang
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Hong Yan
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Guanmao Chen
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Shuming Zhong
- Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Pan Chen
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Hui Zhong
- Biomedical Translational Research Institute, Jinan University, 510630, Guangzhou, China
| | - Hengwen Yang
- Biomedical Translational Research Institute, Jinan University, 510630, Guangzhou, China
| | - Yanbin Jia
- Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhinan Yin
- Biomedical Translational Research Institute, Jinan University, 510630, Guangzhou, China
| | - Jiaying Gong
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
- Department of Radiology, Six Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li Huang
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China
| | - Ying Wang
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China.
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.
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25
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Xie Y, Zhu H, Yuan Y, Guan X, Xie Q, Dong Z. Baseline gut microbiota profiles affect treatment response in patients with depression. Front Microbiol 2024; 15:1429116. [PMID: 39021622 PMCID: PMC11251908 DOI: 10.3389/fmicb.2024.1429116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/20/2024] [Indexed: 07/20/2024] Open
Abstract
The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota.
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Affiliation(s)
- Yingjing Xie
- West China Hospital, Sichuan University, Chengdu, China
| | - Hanwen Zhu
- West China Hospital, Sichuan University, Chengdu, China
| | - Yanling Yuan
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China
| | - Xuan Guan
- Chengdu Medical College, Chengdu, China
| | - Qinglian Xie
- Department of Outpatient, West China Hospital, Sichuan University, Chengdu, China
| | - Zaiquan Dong
- Department of Psychiatry and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, China
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26
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Mao Q, Zhang H, Zhang Z, Lu Y, Pan J, Guo D, Huang L, Tian H, Ma K. Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155510. [PMID: 38696921 DOI: 10.1016/j.phymed.2024.155510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 02/20/2024] [Accepted: 03/01/2024] [Indexed: 05/04/2024]
Abstract
BACKGROUND Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear. PURPOSE This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA. METHODS Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT). RESULTS LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA. CONCLUSION The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.
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Affiliation(s)
- Qiancheng Mao
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Hongxiu Zhang
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China; Institute of Virology, Jinan Municipal Center for Disease Control and Prevention, Jinan 250021, PR China
| | - Zhe Zhang
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Yanting Lu
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Jin Pan
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Dongjing Guo
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Liuxuan Huang
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Haoquan Tian
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Ke Ma
- Shandong Co-Innovation Center of Classic TCM Formula, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
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27
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Engler-Chiurazzi E. B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression. Front Cell Neurosci 2024; 18:1360242. [PMID: 38650657 PMCID: PMC11033448 DOI: 10.3389/fncel.2024.1360242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 03/25/2024] [Indexed: 04/25/2024] Open
Abstract
The immune system has emerged as a key regulator of central nervous system (CNS) function in health and in disease. Importantly, improved understanding of immune contributions to mood disorders has provided novel opportunities for the treatment of debilitating stress-related mental health conditions such as major depressive disorder (MDD). Yet, the impact to, and involvement of, B lymphocytes in the response to stress is not well-understood, leaving a fundamental gap in our knowledge underlying the immune theory of depression. Several emerging clinical and preclinical findings highlight pronounced consequences for B cells in stress and MDD and may indicate key roles for B cells in modulating mood. This review will describe the clinical and foundational observations implicating B cell-psychological stress interactions, discuss potential mechanisms by which B cells may impact brain function in the context of stress and mood disorders, describe research tools that support the investigation of their neurobiological impacts, and highlight remaining research questions. The goal here is for this discussion to illuminate both the scope and limitations of our current understanding regarding the role of B cells, stress, mood, and depression.
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Affiliation(s)
- Elizabeth Engler-Chiurazzi
- Department of Neurosurgery and Neurology, Clinical Neuroscience Research Center, Tulane Brain Institute, Tulane University School of Medicine, New Orleans, LA, United States
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28
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Ķimse L, Reinis A, Miķelsone-Jansone L, Gintere S, Krūmiņa A. A Narrative Review of Psychobiotics: Probiotics That Influence the Gut-Brain Axis. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:601. [PMID: 38674247 PMCID: PMC11051712 DOI: 10.3390/medicina60040601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024]
Abstract
Mental health disorders and dementia have become a serious public health concern, with a heightened frequency of diagnoses observed in the wake of the global COVID-19 pandemic. Psychobiotics, a novel area of research at the intersection of microbiology and neuroscience, explore the potential of probiotics to influence the nervous system and mental health outcomes. This review explores the intricate mechanisms by which psychobiotics interact with the gut-brain axis, shedding light on their effects on mood, cognition, and the stress response. Through a comprehensive analysis of the current literature and recent advancements, we discuss the therapeutic potential of psychobiotics in various mental health disorders, including depression, anxiety, and neurodegenerative diseases like dementia. The findings from this research highlight the promising potential of psychobiotics as innovative interventions in mental health treatment. Further investigation into their mechanisms of action and clinical applications is warranted to fully realize their therapeutic benefits.
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Affiliation(s)
- Laima Ķimse
- Institute of Food Safety, Animal Health and Environment “BIOR”, 1076 Riga, Latvia
| | - Aigars Reinis
- Department of Biology and Microbiology, Riga Stradins University, 1007 Riga, Latvia
| | | | - Sandra Gintere
- Department of Family Medicine, Riga Stradins University, 1007 Riga, Latvia
| | - Angelika Krūmiņa
- Institute of Food Safety, Animal Health and Environment “BIOR”, 1076 Riga, Latvia
- Department of Infectology, Riga Stradins University, 1007 Riga, Latvia
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29
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Dziedzic A, Maciak K, Bliźniewska-Kowalska K, Gałecka M, Kobierecka W, Saluk J. The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota-Gut-Brain Axis: A Literature Review. Nutrients 2024; 16:1054. [PMID: 38613087 PMCID: PMC11013390 DOI: 10.3390/nu16071054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/28/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
The microbiota-gut-brain (MGB) axis is a complex communication network linking the gut, microbiota, and brain, influencing various aspects of health and disease. Dysbiosis, a disturbance in the gut microbiome equilibrium, can significantly impact the MGB axis, leading to alterations in microbial composition and function. Emerging evidence highlights the connection between microbiota alterations and neurological and psychiatric disorders, including depression. This review explores the potential of psychobiotics in managing depressive disorders, emphasizing their role in restoring microbial balance and influencing the MGB axis. Psychobiotics exhibit positive effects on the intestinal barrier, immune response, cortisol levels, and the hypothalamic-pituitary-adrenal (HPA) axis. Studies suggest that probiotics may serve as an adjunct therapy for depression, especially in treatment-resistant cases. This review discusses key findings from studies on psychobiotics interventions, emphasizing their impact on the gut-brain axis and mental health. The increasing acceptance of the expanded concept of the MGB axis underscores the importance of microorganisms in mental well-being. As our understanding of the microbiome's role in health and disease grows, probiotics emerge as promising agents for addressing mental health issues, providing new avenues for therapeutic interventions in depressive disorders.
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Affiliation(s)
- Angela Dziedzic
- University of Lodz, Faculty of Biology and Environmental Protection, Department of General Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland; (K.M.); (W.K.); (J.S.)
| | - Karina Maciak
- University of Lodz, Faculty of Biology and Environmental Protection, Department of General Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland; (K.M.); (W.K.); (J.S.)
| | | | - Małgorzata Gałecka
- Department of Psychotherapy, Medical University of Lodz, Aleksandrowska 159, 91-229 Lodz, Poland;
| | - Weronika Kobierecka
- University of Lodz, Faculty of Biology and Environmental Protection, Department of General Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland; (K.M.); (W.K.); (J.S.)
| | - Joanna Saluk
- University of Lodz, Faculty of Biology and Environmental Protection, Department of General Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland; (K.M.); (W.K.); (J.S.)
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30
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Sochacka K, Kotowska A, Lachowicz-Wiśniewska S. The Role of Gut Microbiota, Nutrition, and Physical Activity in Depression and Obesity-Interdependent Mechanisms/Co-Occurrence. Nutrients 2024; 16:1039. [PMID: 38613071 PMCID: PMC11013804 DOI: 10.3390/nu16071039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/14/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
Obesity and depression are interdependent pathological disorders with strong inflammatory effects commonly found worldwide. They determine the health status of the population and cause key problems in terms of morbidity and mortality. The role of gut microbiota and its composition in the treatment of obesity and psychological factors is increasingly emphasized. Published research suggests that prebiotic, probiotic, or symbiotic preparations can effectively intervene in obesity treatment and mood-dysregulation alleviation. Thus, this literature review aims to highlight the role of intestinal microbiota in treating depression and obesity. An additional purpose is to indicate probiotics, including psychobiotics and prebiotics, potentially beneficial in supporting the treatment of these two diseases.
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Affiliation(s)
- Klaudia Sochacka
- Faculty of Medicine and Health Sciences, Calisia University, 62-800 Kalisz, Poland;
| | - Agata Kotowska
- Department of Social Policy, Institute of Sociological Sciences, College of Social Sciences, University of Rzeszow, 35-310 Rzeszow, Poland;
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31
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Zhang Y, Huang K, Duan J, Zhao R, Yang L. Gut microbiota connects the brain and the heart: potential mechanisms and clinical implications. Psychopharmacology (Berl) 2024; 241:637-651. [PMID: 38407637 DOI: 10.1007/s00213-024-06552-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/04/2024] [Indexed: 02/27/2024]
Abstract
Nowadays, high morbidity and mortality of cardiovascular diseases (CVDs) and high comorbidity rate of neuropsychiatric disorders contribute to global burden of health and economics. Consequently, a discipline concerning abnormal connections between the brain and the heart and the resulting disease states, known as psychocardiology, has garnered interest among researchers. However, identifying a common pathway that physicians can modulate remains a challenge. Gut microbiota, a constituent part of the human intestinal ecosystem, is likely involved in mutual mechanism CVDs and neuropsychiatric disorder share, which could be a potential target of interventions in psychocardiology. This review aimed to discuss complex interactions from the perspectives of microbial and intestinal dysfunction, behavioral factors, and pathophysiological changes and to present possible approaches to regulating gut microbiota, both of which are future directions in psychocardiology.
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Affiliation(s)
- Yi Zhang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
| | - Kai Huang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
| | - Jiahao Duan
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
| | - Rong Zhao
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
| | - Ling Yang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
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32
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Mikulska J, Pietrzak D, Rękawek P, Siudaj K, Walczak-Nowicka ŁJ, Herbet M. Celiac disease and depressive disorders as nutritional implications related to common factors - A comprehensive review. Behav Brain Res 2024; 462:114886. [PMID: 38309373 DOI: 10.1016/j.bbr.2024.114886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/23/2024] [Accepted: 01/27/2024] [Indexed: 02/05/2024]
Abstract
Celiac disease (CD) is an immune-mediated disease affecting the small intestine. The only treatment strategy for CD is the gluten-free diet (GFD). One of the more common mental disorders in CD patients is major depressive disorder (MDD). The influence of GFD on the occurrence of MDD symptoms in patients with CD will be evaluated. This diet often reduces nutritional deficiencies in these patients and also helps to reduce depressive symptoms. Both disease entities are often dominated by the same deficiencies of nutrients such as iron, zinc, selenium, iodine, or B and D vitamins. Deficiencies of particular components in CD can favor MDD and vice versa. Gluten can adversely affect the mental state of patients without CD. Also, intestinal microbiota may play an important role in the described process. This work aims to comprehensively assess the common factors involved in the pathomechanisms of MDD and CD, with particular emphasis on nutrient imbalances. Given the complexity of both disease entities, and the many common links, more research related to improving mental health in these patients and the implementation of a GFD would need to be conducted, but it appears to be a viable pathway to improving the quality of life and health of people struggling with CD and MDD. Therefore, probiotics, micronutrients, macronutrients, and vitamin supplements are recommended to reduce the risk of MDD, given that they may alleviate the symptoms of both these disease entities. In turn, in patients with MDD, it is worth considering testing for CD.
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Affiliation(s)
- Joanna Mikulska
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Diana Pietrzak
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Paweł Rękawek
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Krystian Siudaj
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Łucja Justyna Walczak-Nowicka
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland.
| | - Mariola Herbet
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
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33
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Tan Y, Xu M, Lin D. Review of research progress on intestinal microbiota based on metabolism and inflammation for depression. Arch Microbiol 2024; 206:146. [PMID: 38462572 DOI: 10.1007/s00203-024-03866-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 01/14/2024] [Accepted: 01/24/2024] [Indexed: 03/12/2024]
Abstract
Depression is a prevalent mental illness, affecting a significant portion of the global population. Recent research has highlighted the crucial role of the gut microbiota in both metabolic and central nervous health. By reviewing literature from various databases, including Pubmed, Science Direct, Web of Science, and Scopus, spanning the years 2005-2023, a comprehensive search was conducted using keywords such as "Depression" and "Gut Microbiota". The gut microbiota acts as a "second brain" in humans and can communicate bidirectionally with the brain through the Brain-gut-microbiota axis pathway. This communication involves the immune and nervous systems. However, there are challenges in detecting and treating depression effectively. To address these limitations, researchers have been exploring the relationship between gut microbiota and depression. Studies have shown that gut microbial metabolites, such as lipopolysaccharides and short-chain fatty acids, can induce pro-inflammatory cytokines that contribute to neuroinflammation and increase the risk of depression. The kynurenine pathway, triggered by gut microbial metabolites, has also been associated with neuroinflammation. Thus, investigating these microbial metabolites can provide insights into depression treatment. This review focuses on analyzing the connection between gut microbial metabolites, inflammation, and depression. It explores novel mechanisms contributing to depression, specifically focusing on the mediation of inflammation through the release of pro-inflammatory cytokines. The objective is to provide valuable insights into the mechanisms underlying depression and to propose potential treatments.
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Affiliation(s)
- Yunxiang Tan
- School of Life Sciences, Fudan University, Shanghai, 200438, China
- Faculty of Ecology and Environment, Hainan University, Danzhou, 571700, Hainan, China
| | - Mengyu Xu
- Faculty of Ecology and Environment, Hainan University, Danzhou, 571700, Hainan, China
| | - Deng Lin
- School of Life Sciences, Fudan University, Shanghai, 200438, China.
- Greater Bay Area Institute of Precision Medicine, Guangzhou, 511466, Guangdong, China.
- Beijing Research Center for Chinese Classic Science and Technology, Beijing, 102425, China.
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34
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Choi JY, Park SJ, Lee HJ. Healthy and Unhealthy Dietary Patterns of Depressive Symptoms in Middle-Aged Women. Nutrients 2024; 16:776. [PMID: 38542687 PMCID: PMC10974392 DOI: 10.3390/nu16060776] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/01/2024] [Accepted: 03/06/2024] [Indexed: 02/13/2025] Open
Abstract
Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45-69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37-0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30-2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms.
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Affiliation(s)
- Ji-Young Choi
- Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea;
| | - Seon-Joo Park
- Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea;
- Department of Food and Nutrition, College of Bionanotechnology, Gachon University, Seongnam-si 13120, Republic of Korea
| | - Hae-Jeung Lee
- Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea;
- Department of Food and Nutrition, College of Bionanotechnology, Gachon University, Seongnam-si 13120, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
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35
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Chen S, Wang K, Wang H, Gao Y, Nie K, Jiang X, Su H, Tang Y, Lu F, Dong H, Wang Z. The therapeutic effects of saikosaponins on depression through the modulation of neuroplasticity: From molecular mechanisms to potential clinical applications. Pharmacol Res 2024; 201:107090. [PMID: 38309381 DOI: 10.1016/j.phrs.2024.107090] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 01/07/2024] [Accepted: 01/30/2024] [Indexed: 02/05/2024]
Abstract
Depression is a major global health issue that urgently requires innovative and precise treatment options. In this context, saikosaponin has emerged as a promising candidate, offering a variety of therapeutic benefits that may be effective in combating depression. This review delves into the multifaceted potential of saikosaponins in alleviating depressive symptoms. We summarized the effects of saikosaponins on structural and functional neuroplasticity, elaborated the regulatory mechanism of saikosaponins in modulating key factors that affect neuroplasticity, such as inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the brain-gut axis. Moreover, this paper highlights existing gaps in current researches and outlines directions for future studies. A detailed plan is provided for the future clinical application of saikosaponins, advocating for more targeted researches to speed up its transition from preclinical trials to clinical practice.
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Affiliation(s)
- Shen Chen
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ke Wang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hongzhan Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yang Gao
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Kexin Nie
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xinyue Jiang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hao Su
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yueheng Tang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Fuer Lu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hui Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
| | - Zhi Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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36
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Ryguła I, Pikiewicz W, Grabarek BO, Wójcik M, Kaminiów K. The Role of the Gut Microbiome and Microbial Dysbiosis in Common Skin Diseases. Int J Mol Sci 2024; 25:1984. [PMID: 38396663 PMCID: PMC10889245 DOI: 10.3390/ijms25041984] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/28/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Dermatoses are an increasingly common problem, particularly in developed countries. The causes of this phenomenon include genetic factors and environmental elements. More and more scientific reports suggest that the gut microbiome, more specifically its dysbiosis, also plays an important role in the induction and progression of diseases, including dermatological diseases. The gut microbiome is recognised as the largest endocrine organ, and has a key function in maintaining human homeostasis. In this review, the authors will take a close look at the link between the gut-skin axis and the pathogenesis of dermatoses such as atopic dermatitis, psoriasis, alopecia areata, and acne. The authors will also focus on the role of probiotics in remodelling the microbiome and the alleviation of dermatoses.
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Affiliation(s)
- Izabella Ryguła
- Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland;
| | - Wojciech Pikiewicz
- Collegium Medicum—Faculty of Medicine, WSB University, 41-300 Dabrowa Gornicza, Poland; (W.P.); (B.O.G.); (M.W.)
| | - Beniamin Oskar Grabarek
- Collegium Medicum—Faculty of Medicine, WSB University, 41-300 Dabrowa Gornicza, Poland; (W.P.); (B.O.G.); (M.W.)
| | - Michał Wójcik
- Collegium Medicum—Faculty of Medicine, WSB University, 41-300 Dabrowa Gornicza, Poland; (W.P.); (B.O.G.); (M.W.)
| | - Konrad Kaminiów
- Collegium Medicum—Faculty of Medicine, WSB University, 41-300 Dabrowa Gornicza, Poland; (W.P.); (B.O.G.); (M.W.)
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Jirillo E, Palmirotta R, Colella M, Santacroce L. A Bird's-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It? PATHOPHYSIOLOGY 2024; 31:52-67. [PMID: 38390942 PMCID: PMC10885084 DOI: 10.3390/pathophysiology31010005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/24/2024] Open
Abstract
For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm-Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies, i.e., next-generation sequencing and expanded urine culture, the identification of a microbial community in the urine, the so-called urobiota, became possible. Major phyla detected in the urine are represented by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Particularly, the female urobiota is largely represented by Lactobacillus spp., which are very active against urinary pathogenic Escherichia (E.) coli (UPEC) strains via the generation of lactic acid and hydrogen peroxide. Gut dysbiosis accounts for recurrent urinary tract infections (UTIs), so-called gut-bladder axis syndrome with the formation of intracellular bacterial communities in the course of acute cystitis. However, other chronic urinary tract infections are caused by bacterial strains of intestinal derivation. Monomicrobial and polymicrobial infections account for the outcome of acute and chronic UTIs, even including prostatitis and chronic pelvic pain. E. coli isolates have been shown to be more invasive and resistant to antibiotics. Probiotics, fecal microbial transplantation, phage therapy, antimicrobial peptides, and immune-mediated therapies, even including vaccines for the treatment of UTIs, will be described.
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Affiliation(s)
- Emilio Jirillo
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.J.); (R.P.); (L.S.)
| | - Raffaele Palmirotta
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.J.); (R.P.); (L.S.)
| | - Marica Colella
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.J.); (R.P.); (L.S.)
- Doctoral School, eCampus University, 22060 Novedrate, Italy
| | - Luigi Santacroce
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.J.); (R.P.); (L.S.)
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Gusev E, Sarapultsev A. Interplay of G-proteins and Serotonin in the Neuroimmunoinflammatory Model of Chronic Stress and Depression: A Narrative Review. Curr Pharm Des 2024; 30:180-214. [PMID: 38151838 DOI: 10.2174/0113816128285578231218102020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 11/29/2023] [Indexed: 12/29/2023]
Abstract
INTRODUCTION This narrative review addresses the clinical challenges in stress-related disorders such as depression, focusing on the interplay between neuron-specific and pro-inflammatory mechanisms at the cellular, cerebral, and systemic levels. OBJECTIVE We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors. METHODS This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation. RESULTS The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue. CONCLUSION The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.
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Affiliation(s)
- Evgenii Gusev
- Laboratory of Inflammation Immunology, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, Ekaterinburg 620049, Russia
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, Chelyabinsk 454080, Russia
| | - Alexey Sarapultsev
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, Chelyabinsk 454080, Russia
- Laboratory of Immunopathophysiology, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, Ekaterinburg 620049, Russia
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Wang J, Xin J, Xu X, Chen W, Lv Y, Wei Y, Wei X, Li Z, Ding Q, Zhao H, Wen Y, Zhang X, Fang Y, Zu X. Bacopaside I alleviates depressive-like behaviors by modulating the gut microbiome and host metabolism in CUMS-induced mice. Biomed Pharmacother 2024; 170:115679. [PMID: 38113632 DOI: 10.1016/j.biopha.2023.115679] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 10/06/2023] [Accepted: 10/07/2023] [Indexed: 12/21/2023] Open
Abstract
Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis.
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Affiliation(s)
- Jie Wang
- Department of Natural Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China; Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Jiayun Xin
- Department of Natural Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China; Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Xike Xu
- Department of Natural Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China
| | - Wei Chen
- Department of Natural Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China
| | - Yanhui Lv
- Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Yanping Wei
- Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Xintong Wei
- Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zhanhong Li
- Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510640, China
| | - Qianqian Ding
- Department of Natural Medicinal Chemistry, School of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230012, China
| | - Houyu Zhao
- Department of Diving and Hyperbaric Medical Research, Naval Medical Center, Naval Medical University, Shanghai 200433, China
| | - Yukun Wen
- Department of Diving and Hyperbaric Medical Research, Naval Medical Center, Naval Medical University, Shanghai 200433, China
| | - Xiuyun Zhang
- Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| | - Yiqun Fang
- Department of Diving and Hyperbaric Medical Research, Naval Medical Center, Naval Medical University, Shanghai 200433, China.
| | - Xianpeng Zu
- Department of Natural Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
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Mrozek W, Socha J, Sidorowicz K, Skrok A, Syrytczyk A, Piątkowska-Chmiel I, Herbet M. Pathogenesis and treatment of depression: Role of diet in prevention and therapy. Nutrition 2023; 115:112143. [PMID: 37562078 PMCID: PMC10299949 DOI: 10.1016/j.nut.2023.112143] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/20/2023] [Accepted: 06/23/2023] [Indexed: 08/12/2023]
Abstract
In recent years, there has been a significant increase in depression, which is related to, among other things, the COVID-19 pandemic. Depression can be fatal if not treated or if treated inappropriately. Depression is the leading cause of suicide attempts. The disease is multifactorial, and pharmacotherapy often fails to bring satisfactory results. Therefore, increasingly more importance is attached to the natural healing substances and nutrients in food, which can significantly affect the therapy process and prevention of depressive disorders. A proper diet is vital to preventing depression and can be a valuable addition to psychological and pharmacologic treatment. An inadequate diet may reduce the effectiveness of antidepressants or increase their side effects, leading to life-threatening symptoms. This study aimed to review the literature on the pathogenesis of the development and treatment of depression, with particular emphasis on dietary supplements and the role of nutrition in the prevention and treatment of depressive disorders.
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Affiliation(s)
- Weronika Mrozek
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland
| | - Justyna Socha
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland
| | - Klara Sidorowicz
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland
| | - Aleksandra Skrok
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland
| | - Aleksandra Syrytczyk
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland
| | | | - Mariola Herbet
- Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland.
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Magzal F, Turroni S, Fabbrini M, Barone M, Vitman Schorr A, Ofran A, Tamir S. A personalized diet intervention improves depression symptoms and changes microbiota and metabolite profiles among community-dwelling older adults. Front Nutr 2023; 10:1234549. [PMID: 37794974 PMCID: PMC10547149 DOI: 10.3389/fnut.2023.1234549] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 08/21/2023] [Indexed: 10/06/2023] Open
Abstract
Introduction The impact of diet on mental well-being and gut microorganisms in humans is well recognized. However, research on the connections between food nutrients, gut microbiota, and mental health remains limited. To address this, the present study aimed to assess the effects of a personalized diet, based on individual needs and aligned with the Mediterranean diet principles, on depression symptoms, quality of life, nutritional intake, and gut microbiota changes among older adults living in the community. Methods The intervention involved regular visits from a registered dietitian, who provided tailored dietary recommendations. During the 6-month study, participants completed questionnaires to evaluate their depression levels, quality of life, and dietary habits. Additionally, they provided stool samples for analysis of gut microbiota and metabolites. Results The results demonstrated that the personalized dietary intervention reduced depression symptoms and improved the quality of life among older adults. Furthermore, significant changes in the intake of certain nutrients, such as folate, lutein, zeaxanthin, EPA, and DHA, were observed following the intervention. Moreover, the intervention was associated with increased diversity in the gut microbiome and reduced total short-chain fatty acids, the main metabolites produced by gut microorganisms. The study also revealed correlations between food nutrients, gut microbiota, and mental health parameters. Discussion In conclusion, this research highlights the potential advantages of personalized dietary interventions in managing depression and enhancing overall well-being among older populations. It also sheds light on the role of gut microbiota and its metabolites in these effects. The findings offer valuable insights into the significance of nutrition and gut health for mental well-being in older adults.
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Affiliation(s)
- Faiga Magzal
- Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat Shmona, Israel
- Department of Nutrition, Tel Hai College, Upper Galilee, Israel
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Marco Fabbrini
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Monica Barone
- Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | | | - Snait Tamir
- Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat Shmona, Israel
- Department of Nutrition, Tel Hai College, Upper Galilee, Israel
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Picó-Monllor JA, Sala-Segura E, Tobares RA, Moreno-Ochando A, Hernández-Teruel A, Navarro-Lopez V. Influence and Selection of Probiotics on Depressive Disorders in Occupational Health: Scoping Review. Nutrients 2023; 15:3551. [PMID: 37630741 PMCID: PMC10459799 DOI: 10.3390/nu15163551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/06/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Depressive disorders have a major impact on occupational health and are costly to the economy and the healthcare system. Probiotics are live, non-pathogenic micro-organisms that, when ingested in adequate amounts, can colonize the intestinal tract and confer health benefits on the patient. In recent years, numerous studies have described the potential usefulness of certain probiotic strains in the treatment and prevention of depressive disorders, with differing results. In order to evaluate the possible efficacy and safety of these microorganisms in preventing or ameliorating these disorders, we systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, the Cochrane library, Scopus and Web of science, using the descriptors "Occupational health", "Probiotics", "Depressive Disorder" and "Depression" and filters "Humans" and "Clinical Trials". After applying our inclusion and exclusion criteria, 18 studies were accepted for review and critical analysis. Our analysis suggests that a combination of different probiotic strains, most of them from the genus Bifidobacterium sp. and Lactobacillus sp., could be a good mixture as an adjuvant in the treatment of depressive disorders for the working population.
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Affiliation(s)
- José Antonio Picó-Monllor
- Department of Pharmacology, Pediatrics and Organic Chemistry, Faculty of Pharmacy, Miguel Hernández University (UMH), 03202 Elche, Spain
| | - Elena Sala-Segura
- Department of Pharmacology, Pediatrics and Organic Chemistry, Faculty of Pharmacy, Miguel Hernández University (UMH), 03202 Elche, Spain
| | - Romina Alin Tobares
- Department R&D MATCH Biosystems, S.L. Edificio Quórum IV, Miguel Hernandez University Science Park, Avd. de la Universidad s/n, 03202 Elche, Spain; (R.A.T.); (A.M.-O.); (A.H.-T.)
| | - Avelina Moreno-Ochando
- Department R&D MATCH Biosystems, S.L. Edificio Quórum IV, Miguel Hernandez University Science Park, Avd. de la Universidad s/n, 03202 Elche, Spain; (R.A.T.); (A.M.-O.); (A.H.-T.)
| | - Adrián Hernández-Teruel
- Department R&D MATCH Biosystems, S.L. Edificio Quórum IV, Miguel Hernandez University Science Park, Avd. de la Universidad s/n, 03202 Elche, Spain; (R.A.T.); (A.M.-O.); (A.H.-T.)
| | - Vicente Navarro-Lopez
- MiBioPath Research Group, Faculty of Medicine, Catholic University of Murcia (UCAM), Campus de los Jerónimos n 135, 30107 Murcia, Spain;
- Clinical Microbiology and Infectious Disease Unit, Hospital Universitario Vinalopó, Carrer Tonico Sansano Mora 14, 03293 Elche, Spain
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Liu C, Ma N, Feng Y, Zhou M, Li H, Zhang X, Ma X. From probiotics to postbiotics: Concepts and applications. ANIMAL RESEARCH AND ONE HEALTH 2023; 1:92-114. [DOI: 10.1002/aro2.7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 05/24/2023] [Indexed: 01/05/2025]
Abstract
AbstractIn recent years, the important role of gut microbiota in promoting animal health and regulating immune function in livestock and poultry has been widely reported. The issue of animal health problems causes significant economic losses each year. Probiotics and postbiotics have been widely developed as additives due to their beneficial effects in balancing host gut microbiota, enhancing intestinal epithelial barrier, regulating immunity, and whole‐body metabolism. Probiotics and postbiotics are composed of complex ingredients, with different components and compositions having different effects, requiring classification for discussing their mechanisms of action. Probiotics and postbiotics have considerable prospects in preventing various diseases in the livestock industry and animal feed and medical applications. This review highlights the application value of probiotics and postbiotics as potential probiotic products, emphasizing their concept, mechanism of action, and application, to improve the productivity of livestock and poultry.
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Affiliation(s)
- Chunchen Liu
- College of Public Health North China University of Science and Technology Qinhuangdao Hebei China
- State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Beijing China
| | - Ning Ma
- State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Beijing China
| | - Yue Feng
- State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Beijing China
| | - Min Zhou
- State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Beijing China
| | - Huahui Li
- College of Public Health North China University of Science and Technology Qinhuangdao Hebei China
| | - Xiujun Zhang
- College of Public Health North China University of Science and Technology Qinhuangdao Hebei China
| | - Xi Ma
- State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Beijing China
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Nohesara S, Abdolmaleky HM, Thiagalingam S. Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations. Genes (Basel) 2023; 14:1506. [PMID: 37510410 PMCID: PMC10379841 DOI: 10.3390/genes14071506] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/19/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Nutrition and metabolism modify epigenetic signatures like histone acetylation and DNA methylation. Histone acetylation and DNA methylation in the central nervous system (CNS) can be altered by bioactive nutrients and gut microbiome via the gut-brain axis, which in turn modulate neuronal activity and behavior. Notably, the gut microbiome, with more than 1000 bacterial species, collectively contains almost three million functional genes whose products interact with millions of human epigenetic marks and 30,000 genes in a dynamic manner. However, genetic makeup shapes gut microbiome composition, food/nutrient metabolism, and epigenetic landscape, as well. Here, we first discuss the effect of changes in the microbial structure and composition in shaping specific epigenetic alterations in the brain and their role in the onset and progression of major mental disorders. Afterward, potential interactions among maternal diet/environmental factors, nutrition, and gastrointestinal microbiome, and their roles in accelerating or delaying the onset of severe mental illnesses via epigenetic changes will be discussed. We also provide an overview of the association between the gut microbiome, oxidative stress, and inflammation through epigenetic mechanisms. Finally, we present some underlying mechanisms involved in mediating the influence of the gut microbiome and probiotics on mental health via epigenetic modifications.
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Affiliation(s)
- Shabnam Nohesara
- Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02218, USA; (S.N.); (S.T.)
| | - Hamid Mostafavi Abdolmaleky
- Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02218, USA; (S.N.); (S.T.)
- Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA 02215, USA
| | - Sam Thiagalingam
- Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02218, USA; (S.N.); (S.T.)
- Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, MA 02218, USA
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45
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Teng F, Lu Z, Gao F, Liang J, Li J, Tian X, Wang X, Guan H, Wang J. Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression. Sci Rep 2023; 13:11225. [PMID: 37433869 DOI: 10.1038/s41598-023-38444-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 07/08/2023] [Indexed: 07/13/2023] Open
Abstract
Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.
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Affiliation(s)
- Fei Teng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhongwen Lu
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Fei Gao
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jing Liang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jiawen Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Xuanhe Tian
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Xianshuai Wang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Haowei Guan
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jin Wang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
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Hu JJ, Zhang YB, Zheng SF, Chen GR, Lin YX, Kang DZ, Lin ZY, Yao PS. The causal relationship between circulating biomarkersand the risk of bipolar disorder: A two-sample Mendelian randomization study. J Psychiatr Res 2023; 164:66-71. [PMID: 37327502 DOI: 10.1016/j.jpsychires.2023.05.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/27/2023] [Accepted: 05/25/2023] [Indexed: 06/18/2023]
Abstract
OBJECTIVE To identify susceptible biomarkers for the development of bipolar disorder (BD), we conducted a Mendelian Randomization (MR) design to screen circulating proteins for the potential risk of bipolar disorder systematically. METHODS We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of 4782 human circulating proteins on the risk of bipolar disorder. 376 circulating biomarkers were selected in MR estimation (4406 circulating proteins with less than 3 SNPs were excluded) with 5368 European descents. GWAS meta-analysis of the potential role of all-cause bipolar disorder arose from the Psychiatric Genomics Consortium (41,917 cases, 371,549 controls). RESULTS After IVW and sensitivity analysis, 4 circulating proteins having causal effects on bipolar disorder were identified. ISG15, as a key player in the innate immune response, decreased the risk of bipolar disorder causally (OR = 0.92, 95% CI = 0.89-0.94, P = 1.46e-09). Furthermore, MLN decreased the risk of bipolar disorder causally (OR = 0.94, 95% CI = 0.91-0.97, P = 1.04e-04). In addition, SFTPC (OR = 0.91, 95% CI = 0.86-0.96, P = 4.47e-04) and VCY (OR = 0.86, 95% CI = 0.77-0.96, P = 8.55e-03) presented a suggestive association with bipolar disorder. CONCLUSIONS Our findings indicated that ISG15 and MLN showed evidence of causality in bipolar disorder and provided a promising target for the diagnosis and treatment of diseases.
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Affiliation(s)
- Jiao-Jiao Hu
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China
| | - Yi-Bin Zhang
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China
| | - Shu-Fa Zheng
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China
| | - Guo-Rong Chen
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China
| | - Yuan-Xiang Lin
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Fujian Provincial Key Laboratory of Precision Medicine for Cancer, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China
| | - De-Zhi Kang
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Fujian Provincial Key Laboratory of Precision Medicine for Cancer, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
| | - Zhang-Ya Lin
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China; Department of Pain, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
| | - Pei-Sen Yao
- Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
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Kaunang TMD, Setiawan AA, Mayulu N, Leonita I, Wijaya A, Yusuf VM, Mahira MFNA, Yudisthira D, Gunawan WB, Taslim NA, Purnomo AF, Sabrina N, Amalia N, Permatasari HK, Nurkolis F. Are probiotics beneficial for obese patients with major depressive disorder? Opinion for future implications and strategies. Front Nutr 2023; 10:1205434. [PMID: 37324742 PMCID: PMC10264610 DOI: 10.3389/fnut.2023.1205434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 05/09/2023] [Indexed: 06/17/2023] Open
Affiliation(s)
- Theresia M. D. Kaunang
- Department of Mental Health Sciences, Faculty of Medicine, Sam Ratulangi University-Prof. R. D. Kandou General Hospital, Manado, Indonesia
| | | | - Nelly Mayulu
- Department of Nutrition, Universitas Muhammadiyah Manado, Manado, Indonesia
| | - Ivena Leonita
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Afredo Wijaya
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | | | | | - Dewangga Yudisthira
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - William Ben Gunawan
- Alumnus of Nutrition Science, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
| | - Nurpudji Astuti Taslim
- Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Athaya Febriantyo Purnomo
- Department of Urology, Faculty of Medicine, Universitas Brawijaya - Saiful Anwar General Hospital, Malang, Indonesia
- Department of Oncology, University of Oxford, Oxford, United Kingdom
| | - Nindy Sabrina
- Nutrition Program, Faculty of Food Technology and Health, Sahid University of Jakarta, South Jakarta, Indonesia
| | - Nurlinah Amalia
- Biomedical Science Master Program, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Happy Kurnia Permatasari
- Department of Biochemistry and Biomolecular, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Fahrul Nurkolis
- Department of Biological Sciences, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, Indonesia
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48
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Jach ME, Serefko A, Szopa A, Sajnaga E, Golczyk H, Santos LS, Borowicz-Reutt K, Sieniawska E. The Role of Probiotics and Their Metabolites in the Treatment of Depression. Molecules 2023; 28:molecules28073213. [PMID: 37049975 PMCID: PMC10096791 DOI: 10.3390/molecules28073213] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/31/2023] [Accepted: 04/02/2023] [Indexed: 04/08/2023] Open
Abstract
Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.
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Affiliation(s)
- Monika Elżbieta Jach
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynów Street 1I, 20-708 Lublin, Poland
| | - Anna Serefko
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
| | - Aleksandra Szopa
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
| | - Ewa Sajnaga
- Department of Biomedicine and Environmental Research, The John Paul II Catholic University of Lublin, Konstantynów Street 1J, 20-708 Lublin, Poland
| | - Hieronim Golczyk
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynów Street 1I, 20-708 Lublin, Poland
| | - Leandro Soares Santos
- Department of Animal and Rural Technology, State University of Southwest Bahia, Itapetinga 45700-000, BA, Brazil
| | - Kinga Borowicz-Reutt
- Independent Unit of Experimental Neuropathophysiology, Department of Toxicology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Elwira Sieniawska
- Department of Natural Products Chemistry, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
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49
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Zhao S, Hu S, Sun K, Luo L, Zeng L. Long-term Pu-erh tea consumption improves blue light-induced depression-like behaviors. Food Funct 2023; 14:2313-2325. [PMID: 36779860 DOI: 10.1039/d2fo02780a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Blue light emitted by smartphones and tablets at night increases the risk of depression. Pu-erh tea has been reported to reduce the risk of depression by regulating tryptophan metabolism, but its underlying protective mechanism on depression induced by blue light at night (BLAN) remains unclear. In this work, two groups of C57BL6/J mice were given water or 0.25% (w/v) Pu-erh tea for 120 days, followed by a 45-day BLAN treatment (400 lux blue light between 21:00 and 23:00) to simulate blue light emitted from electronic equipment. Our results indicated that BLAN induced depression-like behaviors and gut microbiota disorders in healthy mice. Pu-erh tea intake significantly reshaped the gut microbiome (especially Bifidobacterium) and regulated the metabolism of short-chain fatty acids (SCFAs) which protected the integrity of the intestinal barrier. This improvement further reduced blood-brain barrier (BBB) damage and alleviated neuroinflammation by inhibiting MyD88/NF-κB pathways which finally regulated neurotransmitters such as brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT). Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent BLAN-induced depression-like behaviors by reshaping the gut microbiota and increasing the generation of SCFAs via the gut-brain axis.
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Affiliation(s)
- Sibo Zhao
- College of Food Science, Southwest University, Beibei, Chongqing 400715, China.
| | - Shanshan Hu
- College of Food Science, Southwest University, Beibei, Chongqing 400715, China.
| | - Kang Sun
- College of Food Science, Southwest University, Beibei, Chongqing 400715, China.
| | - Liyong Luo
- College of Food Science, Southwest University, Beibei, Chongqing 400715, China.
| | - Liang Zeng
- College of Food Science, Southwest University, Beibei, Chongqing 400715, China.
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50
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Ray S, Sil S, Kannan M, Periyasamy P, Buch S. Role of the gut-brain axis in HIV and drug abuse-mediated neuroinflammation. ADVANCES IN DRUG AND ALCOHOL RESEARCH 2023; 3:11092. [PMID: 38389809 PMCID: PMC10880759 DOI: 10.3389/adar.2023.11092] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 02/23/2023] [Indexed: 02/24/2024]
Abstract
Drug abuse and related disorders are a global public health crisis affecting millions, but to date, limited treatment options are available. Abused drugs include but are not limited to opioids, cocaine, nicotine, methamphetamine, and alcohol. Drug abuse and human immunodeficiency virus-1/acquired immune deficiency syndrome (HIV-1/AIDS) are inextricably linked. Extensive research has been done to understand the effect of prolonged drug use on neuronal signaling networks and gut microbiota. Recently, there has been rising interest in exploring the interactions between the central nervous system and the gut microbiome. This review summarizes the existing research that points toward the potential role of the gut microbiome in the pathogenesis of HIV-1-linked drug abuse and subsequent neuroinflammation and neurodegenerative disorders. Preclinical data about gut dysbiosis as a consequence of drug abuse in the context of HIV-1 has been discussed in detail, along with its implications in various neurodegenerative disorders. Understanding this interplay will help elucidate the etiology and progression of drug abuse-induced neurodegenerative disorders. This will consequently be beneficial in developing possible interventions and therapeutic options for these drug abuse-related disorders.
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Affiliation(s)
- Sudipta Ray
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
| | - Susmita Sil
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
| | - Muthukumar Kannan
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
| | - Palsamy Periyasamy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
| | - Shilpa Buch
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
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