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Organski AC, Rajwa B, Reddivari A, Jorgensen JS, Cross TWL. Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection. Gut Microbes 2025; 17:2476562. [PMID: 40071861 PMCID: PMC11913384 DOI: 10.1080/19490976.2025.2476562] [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: 10/02/2024] [Revised: 12/17/2024] [Accepted: 03/03/2025] [Indexed: 03/19/2025] Open
Abstract
The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.
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Affiliation(s)
| | - Bartek Rajwa
- Bindley Bioscience, Purdue University, West Lafayette, IN, USA
| | - Anjali Reddivari
- Department of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA
| | - Joan S Jorgensen
- Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, USA
| | - Tzu-Wen L Cross
- Department of Nutrition Science, Purdue University, West Lafayette, IN, USA
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Deng F, Yang D, Qing L, Chen Y, Zou J, Jia M, Wang Q, Jiang R, Huang L. Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases. Neural Regen Res 2025; 20:3095-3112. [PMID: 39589173 PMCID: PMC11881707 DOI: 10.4103/nrr.nrr-d-24-00607] [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: 06/01/2024] [Revised: 08/07/2024] [Accepted: 09/10/2024] [Indexed: 11/27/2024] Open
Abstract
The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
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Affiliation(s)
- Fengcheng Deng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Dan Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lingxi Qing
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Yifei Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Jilian Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Meiling Jia
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Qian Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Runda Jiang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lihua Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Breaking the cycle: Psychological and social dimensions of pediatric functional gastrointestinal disorders. World J Clin Pediatr 2025; 14:103323. [DOI: 10.5409/wjcp.v14.i2.103323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/14/2024] [Accepted: 01/02/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND Functional gastrointestinal disorders (FGIDs) in children present with chronic symptoms like abdominal pain, diarrhea, and constipation without identifiable structural abnormalities. These disorders are closely linked to gut-brain axis dysfunction, altered gut microbiota, and psychosocial stress, leading to psychiatric comorbidities such as anxiety, depression, and behavioral issues. Understanding this bidirectional relationship is crucial for developing effective, holistic management strategies that address physical and mental health.
AIM To examine the psychiatric impacts of FGIDs in children, focusing on anxiety and depression and their association with other neurodevelopmental disorders of childhood, such as attention-deficit/hyperactivity disorder, emphasizing the role of the gut-brain axis, emotional dysregulation, and psychosocial stress. Key mechanisms explored include neurotransmitter dysregulation, microbiota imbalance, central sensitization, heightening stress reactivity, emotional dysregulation, and symptom perception. The review also evaluates the role of family dynamics and coping strategies in exacerbating FGID symptoms and contributing to psychiatric conditions.
METHODS A narrative review was conducted using 328 studies sourced from PubMed, Scopus, and Google Scholar, covering research published over the past 20 years. Inclusion criteria focused on studies examining FGID diagnosis, gut-brain mechanisms, psychiatric comorbidities, and psychosocial factors in pediatric populations. FGIDs commonly affecting children, including functional constipation, abdominal pain, irritable bowel syndrome, gastroesophageal reflux, and cyclic vomiting syndrome, were analyzed concerning their psychological impacts.
RESULTS The review highlights a strong connection between FGIDs and psychiatric symptoms, mediated by gut-brain axis dysfunction, dysregulated microbiota, and central sensitization. These physiological disruptions increase children’s vulnerability to anxiety and depression, while psychosocial factors - such as chronic stress, early-life trauma, maladaptive family dynamics, and ineffective coping strategies - intensify the cycle of gastrointestinal and emotional distress.
CONCLUSION Effective management of FGIDs requires a biopsychosocial approach integrating medical, psychological, and dietary interventions. Parental education, early intervention, and multidisciplinary care coordination are critical in mitigating long-term psychological impacts and improving both gastrointestinal and mental health outcomes in children with FGIDs.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin K Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Governmental Hospitals, Manama 26671, Bahrain
- Medical Microbiology Section, Department of Pathology, The Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel S Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
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Borrego-Ruiz A, Borrego JJ. The role of the gut microbiome in Alzheimer's disease pathophysiology. Curr Opin Neurol 2025; 38:157-162. [PMID: 39916659 DOI: 10.1097/wco.0000000000001352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
PURPOSE OF REVIEW The present review aims to provide an overview of the existing understanding of the role of the gut microbiome in the Alzheimer's disease pathophysiology. RECENT FINDINGS Recent research has highlighted the significant role of the gut microbiome in the pathogenesis of Alzheimer's disease via the gut-brain axis. However, the precise mechanisms by which gut microbiome and its microbial metabolites influence brain function are not clearly understood. Various factors, such as diet, drugs, lifestyle, stress, and microbial infections can provoke an imbalance in the gut microbiome homeostasis, known as dysbiosis. This dysbiosis impacts intestinal and blood-brain barrier permeability, elevating pro-inflammatory cytokines and contributing to neurodegeneration. Moreover, the gut microbiome generates neurotransmitters, amyloids, neurotoxins, and metabolites, which may play a role in systemic inflammation and in the disruption of physiological barriers. SUMMARY In the past decade, advancements in microbiome analysis technologies and bioinformatics have significantly enhanced our understanding of the role of the gut microbiome in Alzheimer's disease. The gut microbiome plays a pivotal regulatory role in the progression of Alzheimer's disease, and closely interacts with its pathogenesis, encompassing inflammation, amyloidosis, neurodegeneration, tauopathy, and co-pathologies.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), Madrid
| | - Juan J Borrego
- Departamento de Microbiología, Universidad de Málaga, Málaga, Spain
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Attiq A. Early-life antibiotic exposures: Paving the pathway for dysbiosis-induced disorders. Eur J Pharmacol 2025; 991:177298. [PMID: 39864578 DOI: 10.1016/j.ejphar.2025.177298] [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: 11/17/2024] [Revised: 01/06/2025] [Accepted: 01/22/2025] [Indexed: 01/28/2025]
Abstract
Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.
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Affiliation(s)
- Ali Attiq
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Penang, Malaysia.
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Lin D, Howard A, Raihane AS, Di Napoli M, Cáceres E, Ortiz M, Davis J, Abdelrahman AN, Divani AA. Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes. Curr Neurol Neurosci Rep 2025; 25:23. [PMID: 40087204 DOI: 10.1007/s11910-025-01410-0] [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] [Accepted: 02/20/2025] [Indexed: 03/17/2025]
Abstract
PURPOSE OF REVIEW A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI). RECENT FINDINGS The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.
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Affiliation(s)
- Derek Lin
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Andrea Howard
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Ahmed S Raihane
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Mario Di Napoli
- Neurological Service, dell'Annunziata Hospital, Sulmona, L'Aquila, Italy
| | - Eder Cáceres
- Bioscience, School of Engineering, Universidad de La Sabana, Chía, Colombia
- Department of Critical Care, Clínica Universidad de La Sabana, Chía, Colombia
- Unisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia
| | - Michael Ortiz
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Justin Davis
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Allae N Abdelrahman
- School of Medicine, University of New Mexico, Albuquerque, NM, USA
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA
| | - Afshin A Divani
- Department of Neurology, University of New Mexico, MSC10-5620, Albuquerque, NM, 87131, USA.
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Garg G, Trisal A, Singh AK. Unlocking the therapeutic potential of gut microbiota for preventing and treating aging-related neurological disorders. Neuroscience 2025; 572:190-203. [PMID: 40073931 DOI: 10.1016/j.neuroscience.2025.03.020] [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: 09/10/2024] [Revised: 03/03/2025] [Accepted: 03/08/2025] [Indexed: 03/14/2025]
Abstract
Billions of microorganisms inhabit the human gut and maintain overall health. Recent research has revealed the intricate interaction between the brain and gut microbiota through the microbiota-gut-brain axis (MGBA) and its effect on neurodegenerative disorders (NDDs). Alterations in the gut microbiota, known as gut dysbiosis, are linked to the development and progression of several NDDs. Studies suggest that the gut microbiota may be a viable target for improving cognitive health and reducing hallmarks of brain aging. Numerous pathways including hypothalamic-pituitary-adrenal axis stimulation, neurotransmitter release disruption, system-wide inflammation, and increased intestinal and blood-brain barrier permeability connect gut dysbiosis to neurological conditions. Metabolites produced by the gut microbiota influence neural processes that affect brain function. Clinical interventions depend on the capacity to understand the equilibrium between beneficial and detrimental gut microbiota, as it affects both neurodegeneration and neuroprotection. The importance of the gut microbiota and its metabolites during brain aging and the development of neurological disorders is summarized in this review. Moreover, we explored the possible therapeutic effects of the gut microbiota on age-related NDDs. Highlighting various pathways that connect the gut and the brain, this review identifies several important domains where gut microbiota-based interventions could offer possible solutions for age-related NDDs. Furthermore, prebiotics and probiotics are discussed as effective alternatives for mitigating indirect causes of gut dysbiosis. These therapeutic interventions are poised to play a significant role in improving dysbiosis and NDDs, paving the way for further research.
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Affiliation(s)
- Geetika Garg
- Department of Zoology, Savitribai Phule Pune University, Pune 411007, India
| | - Anchal Trisal
- Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Abhishek Kumar Singh
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal 576 104, India.
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Wang M, Liu Y, Zhong L, Wu F, Wang J. Advancements in the investigation of gut microbiota-based strategies for stroke prevention and treatment. Front Immunol 2025; 16:1533343. [PMID: 40103814 PMCID: PMC11914130 DOI: 10.3389/fimmu.2025.1533343] [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: 11/23/2024] [Accepted: 02/11/2025] [Indexed: 03/20/2025] Open
Abstract
Stroke represents a predominant cause of mortality and disability on a global scale, impacting millions annually and exerting a considerable strain on healthcare systems. The incidence of stroke exhibits regional variability, with ischemic stroke accounting for the majority of occurrences. Post-stroke complications, such as cognitive impairment, motor dysfunction, and recurrent stroke, profoundly affect patients' quality of life. Recent advancements have elucidated the microbiota-gut-brain axis (MGBA), underscoring the complex interplay between gut health and brain function. Dysbiosis, characterized by an imbalance in gut microbiota, is significantly linked to an elevated risk of stroke and unfavorable outcomes. The MGBA plays a crucial role in modulating immune function, neurotransmitter levels, and metabolic byproducts, which may intensify neuroinflammation and impair cerebral health. This review elucidates the role of MGBA in stroke pathophysiology and explores potential gut-targeted therapeutic strategies to reduce stroke risk and promote recovery, including probiotics, prebiotics, pharmacological interventions, and dietary modifications. However, the current prevention and treatment strategies based on intestinal flora still face many problems, such as the large difference of individual intestinal flora, the stability of efficacy, and the long-term safety need to be considered. Further research needs to be strengthened to promote its better application in clinical practice.
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Affiliation(s)
- Min Wang
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
| | - Yan Liu
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
| | - Li Zhong
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
| | - Fang Wu
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
| | - Jinjin Wang
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China
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Tofani GSS, Clarke G, Cryan JF. I "Gut" Rhythm: the microbiota as a modulator of the stress response and circadian rhythms. FEBS J 2025; 292:1454-1479. [PMID: 39841560 PMCID: PMC11927059 DOI: 10.1111/febs.17400] [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: 08/02/2024] [Revised: 11/20/2024] [Accepted: 01/07/2025] [Indexed: 01/24/2025]
Abstract
Modern habits are becoming more and more disruptive to health. As our days are often filled with circadian disruption and stress exposures, we need to understand how our responses to these external stimuli are shaped and how their mediators can be targeted to promote health. A growing body of research demonstrates the role of the gut microbiota in influencing brain function and behavior. The stress response and circadian rhythms, which are essential to maintaining appropriate responses to the environment, are known to be impacted by the gut microbiota. Gut microbes have been shown to alter the host's response to stress and modulate circadian rhythmicity. Although studies demonstrated strong links between the gut microbiota, circadian rhythms and the stress response, such studies were conducted in an independent manner not conducive to understanding the interface between these factors. Due to the interconnected nature of the stress response and circadian rhythms, in this review we explore how the gut microbiota may play a role in regulating the integration of stress and circadian signals in mammals and the consequences for brain health and disease.
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Affiliation(s)
- Gabriel S S Tofani
- APC Microbiome, University College Cork, Ireland
- Department of Anatomy & Neuroscience, University College Cork, Ireland
| | - Gerard Clarke
- APC Microbiome, University College Cork, Ireland
- Department of Psychiatry & Neurobehavioural Science, University College Cork, Ireland
| | - John F Cryan
- APC Microbiome, University College Cork, Ireland
- Department of Anatomy & Neuroscience, University College Cork, Ireland
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Ho T, Elma Ö, Kocanda L, Brain K, Lam T, Kanhere T, Dong HJ. The brain-gut axis and chronic pain: mechanisms and therapeutic opportunities. Front Neurosci 2025; 19:1545997. [PMID: 40027466 PMCID: PMC11868272 DOI: 10.3389/fnins.2025.1545997] [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: 12/16/2024] [Accepted: 01/29/2025] [Indexed: 03/05/2025] Open
Abstract
The brain-gut axis (BGA) is emerging as a critical mediator in chronic pain, involving bidirectional communication between the central nervous system and the gastrointestinal system. The "Pain Matrix" is associated with microbial dysbiosis, vagus nerve dysfunction, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, driving neuroinflammation and central sensitization. Key mechanisms include microbial diversity loss, leaky gut, and altered neuroactive signaling via short-chain fatty acids (SCFAs) and vagal pathways. This narrative review explores the intricate interplay between BGA mechanisms and chronic pain, highlighting therapeutic opportunities such as restoring dysbiosis, modulating vagus nerve activity, and regulating endocrine pathways. These interventions target inflammation, autonomic balance, and stress/reward pathway modulation, offering a promising path toward integrative pain management. Further research is required to validate these strategies and improve patient outcomes.
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Affiliation(s)
- Tim Ho
- Faculty of Medicine and Health, Sydney Medical School, Westmead Clinical School, The University of Sydney, Sydney, Australia
| | - Ömer Elma
- Unit of Physiotherapy, Department of Rehabilitation and Sport Sciences, Faculty of Health and Social Sciences, Bournemouth University, Bournemouth, United Kingdom
- Pain in Motion International Research Group, Vrije Universiteit Brussels, Brussels, Belgium
| | - Lucy Kocanda
- Department of Rural Health, College of Health, Medicine and Wellbeing, University of Newcastle, Tamworth, NSW, Australia
- Tamworth Integrated Pain Service, Hunter New England Local Health District, Tamworth, NSW, Australia
- Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Katherine Brain
- Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- Hunter Integrated Pain Service, Hunter New England Local Health District, New Lambton Heights, NSW, Australia
- School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
| | - Thao Lam
- Faculty of Medicine and Health, Sydney Medical School, Westmead Clinical School, The University of Sydney, Sydney, Australia
| | - Tejas Kanhere
- Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
| | - Huan-Ji Dong
- Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
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Cheng Y, Hu G, Deng L, Zan Y, Chen X. Therapeutic role of gut microbiota in lung injury-related cognitive impairment. Front Nutr 2025; 11:1521214. [PMID: 40017811 PMCID: PMC11867030 DOI: 10.3389/fnut.2024.1521214] [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: 11/01/2024] [Accepted: 12/16/2024] [Indexed: 03/01/2025] Open
Abstract
Lung injury can lead to specific neurocognitive dysfunction, and the "triple-hit" phenomenon may be the key theoretical mechanism for the progressive impairment of lung injury-related cognitive impairment. The lung and brain can communicate biologically through immune regulation pathway, hypoxic pathway, neural circuit, mitochondrial dysfunction, and microbial influence, which is called the "lung-brain axis." The gut microbiota is a highly complex community of microorganisms that reside in the gut and communicate with the lung via the "gut-lung axis." The dysregulation of gut microbiota may lead to the migration of pathogenic bacteria to the lung, and directly or indirectly regulate the lung immune response through their metabolites, which may cause or aggravate lung injury. The gut microbiota and the brain interact through the "gut-brain axis." The gut microbiota can influence and regulate cognitive function and behavior of the brain through neural pathway mechanisms, immune regulation pathway and hypothalamic-pituitary-adrenal (HPA) axis regulation. Based on the gut microbiota regulation mechanism of the "gut-lung axis" and "gut-brain axis," combined with the mechanisms of cognitive impairment caused by lung injury, we proposed the "triple-hit" hypothesis. It states that the pathophysiological changes of lung injury trigger a series of events such as immune disorder, inflammatory responses, and microbiota changes, which activate the "lung-gut axis," thus forming a "triple-hit" that leads to the development or deterioration of cognitive impairment. This hypothesis provides a more comprehensive framework for studying and understanding brain dysfunction in the context of lung injury. This review proposes the existence of an interactive tandem network for information exchange among the gut, lung, and brain, referred to as the "gut-lung-brain axis." It further explores the potential mechanism of lung injury-related cognitive impairment caused by multiple interactions of gut microbiota in the "gut-lung-brain axis." We found that there are many numerous pathophysiological factors that influence the interaction within the "gut-lung-brain axis." The impact of gut microbiota on cognitive functions related to lung injury may be mediated through mechanisms such as the "triple-hit" hypothesis, direct translocation of microbes and their metabolites, hypoxic pathway, immune modulation, vagal nerve activity, and the HPA axis regulation, among others. As the research deepens, based on the "triple-hit" hypothesis of lung injury, it is further discovered that gut microbial therapy can significantly change the pathogenesis of the inflammatory process on the "gut-lung-brain axis." It can also relieve lung injury and therapeutically modulate brain function and behavior. This perspective provides a new idea for the follow-up treatment of lung injury-related cognitive impairment caused by dysregulation of gut microbiota.
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Affiliation(s)
| | | | | | | | - Xia Chen
- Department of Pediatrics, Child and Adolescent Psychiatric Center of Jiangbei Campus, The First Affiliated Hospital of Army Medical University (Army 958th Hospital), Chongqing, China
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Paul JK, Azmal M, Haque ANMSNB, Meem M, Talukder OF, Ghosh A. Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases. World J Gastroenterol 2025; 31:99913. [PMID: 39926224 PMCID: PMC11718612 DOI: 10.3748/wjg.v31.i5.99913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/25/2024] [Accepted: 12/05/2024] [Indexed: 12/30/2024] Open
Abstract
The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.
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Affiliation(s)
- Jibon Kumar Paul
- Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Mahir Azmal
- Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - ANM Shah Newaz Been Haque
- Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Meghla Meem
- Faculty of Medicine, Dhaka University, Dhaka 1000, Bangladesh
| | - Omar Faruk Talukder
- Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Ajit Ghosh
- Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
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13
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Gao A, Lv J, Su Y. The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis. Brain Sci 2025; 15:159. [PMID: 40002492 PMCID: PMC11853208 DOI: 10.3390/brainsci15020159] [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: 01/07/2025] [Revised: 01/30/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.
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Affiliation(s)
| | | | - Yanwei Su
- Department of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (A.G.); (J.L.)
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14
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Țenea-Cojan ȘT, Dinescu VC, Gheorman V, Dragne IG, Gheorman V, Forțofoiu MC, Fortofoiu M, Dobrinescu AG. Exploring Multidisciplinary Approaches to Comorbid Psychiatric and Medical Disorders: A Scoping Review. Life (Basel) 2025; 15:251. [PMID: 40003660 PMCID: PMC11856229 DOI: 10.3390/life15020251] [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: 12/16/2024] [Revised: 01/19/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025] Open
Abstract
Psychiatric disorders often coexist with internal medical conditions, posing significant challenges to diagnosis, treatment, and overall patient outcomes. This study examines the bidirectional relationship between these conditions, emphasizing their impact on morbidity, treatment adherence, and quality of life. Through a comprehensive review of the peer-reviewed literature, we explore the physiological, neuroinflammatory, and psychosocial mechanisms that underpin these interactions. Key psychiatric disorders, including depression, anxiety, cognitive impairments, and psychosis, are identified as critical contributors to diagnostic complexity and therapeutic hurdles. Our findings underscore the importance of integrated, multidisciplinary care models, advocating for early detection, routine mental health screening, and personalized treatment strategies. Challenges such as overlapping symptoms, diagnostic ambiguities, and potential drug interactions are critically analyzed, with practical, evidence-based recommendations proposed for clinical practice. Despite advancements, significant research gaps persist, particularly the lack of longitudinal studies and the limited application of precision medicine tailored to this population. Future directions focus on enhancing diagnostic tools, developing innovative therapeutic approaches, and integrating mental health services into routine care. This study highlights the critical need for holistic, patient-centered approaches to manage comorbid psychiatric and internal medical conditions, offering actionable insights to improve outcomes and bridge existing gaps in research and practice.
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Affiliation(s)
| | - Venera-Cristina Dinescu
- Department of Health Promotion and Occupational Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Veronica Gheorman
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | | | - Victor Gheorman
- Department of Psychiatry I, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Mircea-Cătălin Forțofoiu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Maria Fortofoiu
- Department of Emergency Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Adrian Gabriel Dobrinescu
- Department of Thoracic Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
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15
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Bertollo AG, Santos CF, Bagatini MD, Ignácio ZM. Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front Neurosci 2025; 19:1541075. [PMID: 39981404 PMCID: PMC11839829 DOI: 10.3389/fnins.2025.1541075] [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: 12/06/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.
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16
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Villablanca EJ. Organismal mucosal immunology: A perspective through the eyes of game theory. Mucosal Immunol 2025; 18:16-25. [PMID: 39672543 DOI: 10.1016/j.mucimm.2024.12.003] [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: 06/23/2024] [Revised: 12/03/2024] [Accepted: 12/06/2024] [Indexed: 12/15/2024]
Abstract
In complex organisms, functional units must interact cohesively to maintain homeostasis, especially within mucosal barriers that house diverse, specialized cell exposed to constant environmental challenges. Understanding how homeostasis at mucosal barriers is maintained and how its disruption can lead to autoimmune diseases or cancer, requires a holistic view. Although omics approaches and systems immunology have become powerful tools, they are not without limitations; interpretations may reflect researchers' assumptions, even if other explanations exist. In this perspective, I propose that applying game theory concepts to mucosal immunology could help interpret complex data, offering fresh perspectives and supporting the exploration of alternative scenarios. By framing the mucosal immune system as a network of strategic interactions with multiple possible outcomes, game theory, which analyzes strategic interactions and decision-making processes, could illuminate novel cell types and functions, cell interactions, and responses to pathogens and commensals, leading to a more comprehensive understanding of immune homeostasis and diseases. In addition, game theory might encourage researchers to consider a broader range of possibilities, reduce the risk of myopic thinking, and ultimately enable a more refined and comprehensive understanding of the complexity of the immune system at mucosal barriers. This perspective aims to introduce game theory as a complementary framework for mucosal immunologists, encouraging them to incorporate these concepts into data interpretation and system modeling.
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Affiliation(s)
- Eduardo J Villablanca
- Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institute and University Hospital, Stockholm, Sweden; Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden; Center of Molecular Medicine, Stockholm, Sweden.
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17
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Jiao F, Zhou L, Wu Z. The microbiota-gut-brain axis: a potential target in the small-molecule compounds and gene therapeutic strategies for Parkinson's disease. Neurol Sci 2025; 46:561-578. [PMID: 39546084 PMCID: PMC11772541 DOI: 10.1007/s10072-024-07878-x] [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: 08/02/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUNDS Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD. OBJECTIVES In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD. CONCLUSIONS Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.
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Affiliation(s)
- Fengjuan Jiao
- School of Mental Health, Jining Medical University, No. 45, Jianshe South Road, Jining City, Shandong Province, 272067, P. R. China.
- Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, P. R. China.
| | - Lincong Zhou
- School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272067, PR China
| | - Zaixin Wu
- School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272067, PR China
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18
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Marwaha K, Cain R, Asmis K, Czaplinski K, Holland N, Mayer DCG, Chacon J. Exploring the complex relationship between psychosocial stress and the gut microbiome: implications for inflammation and immune modulation. J Appl Physiol (1985) 2025; 138:518-535. [PMID: 39813028 DOI: 10.1152/japplphysiol.00652.2024] [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: 08/22/2024] [Revised: 12/16/2024] [Accepted: 01/07/2025] [Indexed: 01/16/2025] Open
Abstract
There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a proinflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of natural killer (NK) cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as interleukin-1, interleukin-6, tumor necrotic factor-α, interferon-gamma. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a proinflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.
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Affiliation(s)
- Komal Marwaha
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Ryan Cain
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Katherine Asmis
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Katya Czaplinski
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Nathan Holland
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Darly C Ghislaine Mayer
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
| | - Jessica Chacon
- Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas, United States
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19
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Abavisani M, Faraji N, Ebadpour N, Kesharwani P, Sahebkar A. Beyond digestion: Exploring how the gut microbiota modulates human social behaviors. Neuroscience 2025; 565:52-62. [PMID: 39615647 DOI: 10.1016/j.neuroscience.2024.11.068] [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: 09/10/2024] [Revised: 11/23/2024] [Accepted: 11/25/2024] [Indexed: 01/07/2025]
Abstract
For a long time, traditional medicine has acknowledged the gut's impact on general health. Contemporary science substantiates this association through investigations of the gut microbiota, the extensive community of microorganisms inhabiting our gastrointestinal system. These microscopic residents considerably improve digestive processes, nutritional absorption, immunological function, and pathogen defense. Nevertheless, a variety of gastrointestinal and extra-intestinal disorders can result from dysbiosis, an imbalance of the microbial composition of the gut microbiota. A groundbreaking discovery is the gut-brain axis, a complex communication network that links the enteric and central nervous system (CNS). This bidirectional communication allows the brain to influence gut activities and vice versa, impacting mental health and mood disorders like anxiety and depression. The gut microbiota can influence this communication by creating neurotransmitters and short-chain fatty acids, among other biochemical processes. These factors may affect our mental state, our ability to regulate our emotions, and the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to explore the complex interrelationships between the brain and the gut microbiota. We also conducted a thorough examination of the existing understanding in the area of how microbiota affects social behaviors, including emotions, stress responses, and cognitive functions. We also explored the potential of interventions that focus on the connection between the gut and the brain, such as using probiotics to treat diseases of the CNS. This research opens up new possibilities for addressing mental health and neurological conditions in an innovative manner.
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Affiliation(s)
- Mohammad Abavisani
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Navid Faraji
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negar Ebadpour
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran.
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20
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Osama A, Anwar AM, Ezzeldin S, Ahmed EA, Mahgoub S, Ibrahim O, Ibrahim SA, Abdelhamid IA, Bakry U, Diab AA, A Sayed A, Magdeldin S. Integrative multi-omics analysis of autism spectrum disorder reveals unique microbial macromolecules interactions. J Adv Res 2025:S2090-1232(25)00055-4. [PMID: 39870302 DOI: 10.1016/j.jare.2025.01.036] [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: 08/31/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 01/29/2025] Open
Abstract
INTRODUCTION Gut microbiota alterations have been implicated in Autism Spectrum Disorder (ASD), yet the mechanisms linking these changes to ASD pathophysiology remain unclear. OBJECTIVES This study utilized a multi-omics approach to uncover mechanisms linking gut microbiota to ASD by examining microbial diversity, bacterial metaproteins, associated metabolic pathways and host proteome. METHODS The gut microbiota of 30 children with severe ASD and 30 healthy controls was analyzed. Microbial diversity was assessed using 16S rRNA V3 and V4 sequencing. A novel metaproteomics pipeline identified bacterial proteins, while untargeted metabolomics explored altered metabolic pathways. Finally, multi-omics integration was employed to connect macromolecular changes to neurodevelopmental deficits. RESULTS Children with ASD exhibited significant alterations in gut microbiota, including lower diversity and richness compared to controls. Tyzzerella was uniquely associated with the ASD group. Microbial network analysis revealed rewiring and reduced stability in ASD. Major metaproteins identified were produced by Bifidobacterium and Klebsiella (e.g., xylose isomerase and NADH peroxidase). Metabolomics profiling identified neurotransmitters (e.g., glutamate, DOPAC), lipids, and amino acids capable of crossing the blood-brain barrier, potentially contributing to neurodevelopmental and immune dysregulation. Host proteome analysis revealed altered proteins, including kallikrein (KLK1) and transthyretin (TTR), involved in neuroinflammation and immune regulation. Finally, multi-omics integration supported single-omics findings and reinforced the hypothesis that gut microbiota and their macromolecular products may contribute to ASD-associated symptoms. CONCLUSIONS The integration of multi-omics data provided critical evidence that alteration in gut microbiota and associated macromolecule production may play a role in ASD-related symptoms and co-morbidities. Key bacterial metaproteins and metabolites were identified as potential contributors to neurological and immune dysregulation in ASD, underscoring possible novel targets for therapeutic intervention.
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Affiliation(s)
- Aya Osama
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt
| | - Ali Mostafa Anwar
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt
| | - Shahd Ezzeldin
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt
| | - Eman Ali Ahmed
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt; Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt
| | - Sebaey Mahgoub
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt
| | - Omneya Ibrahim
- Psychiatry and Neurology Department, Faculty of Medicine, Suez Canal University, Egypt
| | | | | | - Usama Bakry
- Egypt Center for Research and Regenerative Medicine (ECRRM), Egypt
| | - Aya A Diab
- Genomic Research Program, Basic Research Department, Children's Cancer Hospital Egypt 57357, 11441 Cairo, Egypt
| | - Ahmed A Sayed
- Genomic Research Program, Basic Research Department, Children's Cancer Hospital Egypt 57357, 11441 Cairo, Egypt; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Sameh Magdeldin
- Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt; Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt.
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21
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McGrew K, de Oca NM, Kosten TA. Effect of Relocation, Social Housing Changes, and Diarrhea Status on Microbiome Composition of Juvenile Cynomolgus Macaques ( Macaca fascicularis). Microorganisms 2025; 13:98. [PMID: 39858866 PMCID: PMC11767897 DOI: 10.3390/microorganisms13010098] [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: 11/22/2024] [Revised: 12/16/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
Social housing changes are likely stressful and can be associated with diarrhea, the most common health problem noted in captive macaque populations. Diarrhea may reflect a negative shift in the gut flora ("gut dysbiosis"). This study reported on changes in the gut microbiome composition of juvenile primates (Macaca fascicularis) that experienced a change in social housing and exhibited diarrhea. A matched-case-control design was utilized to compare fecal samples from gut-unhealthy animals to healthy counterparts (n = 61). Baseline samples from recently imported animals were collected during routine sedation events. When an animal experienced a housing change, the entire cohort was monitored for diarrhea. Post-relocation samples were collected from animals that exhibited diarrhea and from their matched controls. Samples were assessed via 16S rRNA next-generation sequencing for a microbiome analysis and by ELISA for cortisol levels. Fecal cortisol levels did not differ between groups or across time points. Alpha diversity increased after relocation and differed by sex with males demonstrating a greater change in alpha diversity (p < 0.01). Although exhibiting diarrhea did not affect alpha diversity levels, it was associated with increased beta diversity (p < 0.05). Understanding how the microbiome may be affected by relocation will help guide prevention strategies such as the use of specific probiotics to reduce the incidence of diarrhea.
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Affiliation(s)
- Keely McGrew
- Charles River Laboratories, Inc., Houston, TX 77047, USA; (K.M.); (N.M.d.O.)
- Department of Psychology, University of Houston, Houston, TX 77004, USA
| | - Nicole Monts de Oca
- Charles River Laboratories, Inc., Houston, TX 77047, USA; (K.M.); (N.M.d.O.)
| | - Therese A. Kosten
- Department of Psychology, University of Houston, Houston, TX 77004, USA
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22
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Wu S, Li L, Wang X, Yan Z. Authors' reply to comments on "Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles" by Wu et al. 2024. Oral Dis 2025; 31:326-327. [PMID: 38923630 DOI: 10.1111/odi.15049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024]
Affiliation(s)
- Shuangshuang Wu
- Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Linman Li
- Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Xu Wang
- Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Zhimin Yan
- Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
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23
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Guan W, Qi W, Sheng XM. Evidence for the contribution of vasopressin V1 B receptors in the pathophysiology of depression. Biochem Pharmacol 2025; 231:116672. [PMID: 39608503 DOI: 10.1016/j.bcp.2024.116672] [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: 08/28/2024] [Revised: 11/18/2024] [Accepted: 11/25/2024] [Indexed: 11/30/2024]
Abstract
Depression is a chronic and recurrent psychiatric condition characterised by depressed mood, loss of interest or pleasure, poor sleep, low appetite, and poor concentration. Research has shown that both heritable and environmental risk factors are involved in the pathogenesis of depression. In addition, several studies have indicated that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the development of depression in adulthood. However, the mechanism underlying the activation of HPA axis-induced depression remains unclear. Arginine vasopressin (AVP), also known as vasopressin (VP), is a hormone synthesised in the hypothalamus that plays important roles in numerous biological functions in mammals, including the regulation of stress and anxiety, and has been implicated in the pathogenesis of many disorders. VP regulates pituitary corticotroph function by binding to the plasma membrane G-protein receptors of the V1B receptor (V1BR), which are coupled to calcium-phospholipid signalling. V1BR, a receptor subtype of VP, plays a pivotal role in HPA axis abnormalities observed in depression. In animals, V1BR antagonists reduce plasma stress hormone levels and have been shown to have antidepressant activity. However, the precise mechanism of V1BR in modulating HPA axis activity remains unclear. We therefore reviewed and integrated the clinical and preclinical literature pertinent to the role of V1BR in depression, while emphasising the effect of V1BR antagonists on attenuating the hyperactivity of the HPA axis. In addition, therapy for depression through the regulation of the HPA axis is briefly discussed. Although effective antidepressants are available, a large proportion of patients do not respond to initial treatment. Therefore, this review describes the exact mechanisms of V1BR in depression and contributes to the development of new therapeutic strategies for this disease.
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Affiliation(s)
- Wei Guan
- Department of Pharmacology, Nantong University, Nantong 226001, Jiangsu, China
| | - Wang Qi
- Department of Pharmacology, The First People's Hospital of Yancheng, Yancheng 224000, Jiangsu, China
| | - Xiao-Ming Sheng
- Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
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24
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Patel RA, Panche AN, Harke SN. Gut microbiome-gut brain axis-depression: interconnection. World J Biol Psychiatry 2025; 26:1-36. [PMID: 39713871 DOI: 10.1080/15622975.2024.2436854] [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: 08/07/2024] [Revised: 11/26/2024] [Accepted: 11/28/2024] [Indexed: 12/24/2024]
Abstract
OBJECTIVES The relationship between the gut microbiome and mental health, particularly depression, has gained significant attention. This review explores the connection between microbial metabolites, dysbiosis, and depression. The gut microbiome, comprising diverse microorganisms, maintains physiological balance and influences health through the gut-brain axis, a communication pathway between the gut and the central nervous system. METHODS Dysbiosis, an imbalance in the gut microbiome, disrupts this axis and worsens depressive symptoms. Factors like diet, antibiotics, and lifestyle can cause this imbalance, leading to changes in microbial composition, metabolism, and immune responses. This imbalance can induce inflammation, disrupt neurotransmitter regulation, and affect hormonal and epigenetic processes, all linked to depression. RESULTS Microbial metabolites, such as short-chain fatty acids and neurotransmitters, are key to gut-brain communication, influencing immune regulation and mood. The altered production of these metabolites is associated with depression. While progress has been made in understanding the gut-brain axis, more research is needed to clarify causative relationships and develop new treatments. The emerging field of psychobiotics and microbiome-targeted therapies shows promise for innovative depression treatments by harnessing the gut microbiome's potential. CONCLUSIONS Epigenetic mechanisms, including DNA methylation and histone modifications, are crucial in how the gut microbiota impacts mental health. Understanding these mechanisms offers new prospects for preventing and treating depression through the gut-brain axis.
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Affiliation(s)
- Ruhina Afroz Patel
- Institute of Biosciences and Technology, MGM University, Aurangabad, India
| | - Archana N Panche
- Institute of Biosciences and Technology, MGM University, Aurangabad, India
| | - Sanjay N Harke
- Institute of Biosciences and Technology, MGM University, Aurangabad, India
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Yao M, Qu Y, Zheng Y, Guo H. The effect of exercise on depression and gut microbiota: Possible mechanisms. Brain Res Bull 2025; 220:111130. [PMID: 39557221 DOI: 10.1016/j.brainresbull.2024.111130] [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: 08/31/2024] [Revised: 11/09/2024] [Accepted: 11/12/2024] [Indexed: 11/20/2024]
Abstract
Exercise can effectively prevent and treat depression and anxiety, with gut microbiota playing a crucial role in this process. Studies have shown that exercise can influence the diversity and composition of gut microbiota, which in turn affects depression through immune, endocrine, and neural pathways in the gut-brain axis. The effectiveness of exercise varies based on its type, intensity, and duration, largely due to the different changes in gut microbiota. This article summarizes the possible mechanisms by which exercise affects gut microbiota and how gut microbiota influences depression. Additionally, we reviewed literature on the effects of exercise on depression at different intensities, types, and durations to provide a reference for future exercise-based therapies for depression.
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Affiliation(s)
- Mingchen Yao
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Yaqi Qu
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Yalin Zheng
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Hao Guo
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China.
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26
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Arjun OK, Sethi M, Parida D, Dash J, Kumar Das S, Prakash T, Senapati S. Comprehensive physiological and genomic characterization of a potential probiotic strain, Lactiplantibacillus plantarum ILSF15, isolated from the gut of tribes of Odisha, India. Gene 2024; 931:148882. [PMID: 39182659 DOI: 10.1016/j.gene.2024.148882] [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: 03/18/2024] [Revised: 08/11/2024] [Accepted: 08/21/2024] [Indexed: 08/27/2024]
Abstract
Characterizing probiotic features of organisms isolated from diverse environments can lead to the discovery of novel strains with promising functional features and health attributes. The present study attempts to characterize a novel probiotic strain isolated from the gut of the tribal population of Odisha, India. Based on 16S rRNA-based phylogeny, the strain was identified as a species of the Lactiplantibacillus genus and was named Lactiplantibacillus plantarum strain ILSF15. The current investigation focuses on elucidating this strain's genetic and physiological properties associated with probiotic attributes such as biosafety risk, host adaptation/survival traits, and beneficial functional features. The novel strain was observed, in vitro, exhibiting features such as acid/bile tolerance, adhesion to the host enteric epithelial cells, cholesterol assimilation, and pathogen exclusion, indicating its ability to survive the harsh environment of the human GIT and resist the growth of harmful microorganisms. Additionally, the L. plantarum ILSF15 strain was found to harbor genes associated with the metabolism and synthesis of various bioactive molecules, including amino acids, carbohydrates, lipids, and vitamins, highlighting the organism's ability to efficiently utilize diverse resources and contribute to the host's nutrition and health. Several genes involved in host adaptation/survival strategies and host-microbe interactions were also identified from the ILSF15 genome. Moreover, L. plantarum strains, in general, were found to have an open pangenome characterized by high genetic diversity and the absence of specific lineages associated with particular habitats, signifying its versatile nature and potential applications in probiotic and functional food industries.
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Affiliation(s)
- O K Arjun
- School of Biosciences and Bioengineering, Indian Institute of Technology Mandi, Himachal Pradesh 175005, India
| | - Manisha Sethi
- Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha 751023, India
| | - Deepti Parida
- Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha 751023, India
| | - Jayalaxmi Dash
- Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha 751023, India
| | - Suraja Kumar Das
- Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha 751023, India
| | - Tulika Prakash
- School of Biosciences and Bioengineering, Indian Institute of Technology Mandi, Himachal Pradesh 175005, India.
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Duan ZM, Wu LF. Role of oral-gut-brain axis in psychiatric and neurological disorders. Shijie Huaren Xiaohua Zazhi 2024; 32:878-886. [DOI: 10.11569/wcjd.v32.i12.878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/06/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024] Open
Abstract
The oral cavity and gut are two important microbial habitats in the human body, harboring the most ecologically rich and taxonomically diverse microbial communities in humans, which play a key role in microbiome related diseases. In recent years, the emerging concept of the oral-gut-brain axis has attracted widespread attention in the fields of neuroscience, digestive science, and microbiology. It is not only an anatomical description, but also a comprehensive concept that covers multiple physiological functions and pathological mechanisms. Simply put, the oral-gut-brain axis refers to the complex network that connects the mouth, gut, and brain tightly together through neural connections and hormonal and immune pathways. With the deepening of research on the oral-gut-brain axis theory, more and more evidence shows that it plays an important role in depression, Parkinson's disease, and other neurodegenerative diseases. This article reviews the recent progress in research of the oral-gut-brain axis in psychiatric and neurological diseases.
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Affiliation(s)
- Zhi-Min Duan
- Department of Gastroenterology, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Ling-Fei Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Xie S, Liu M, Li W. Impact of Radiotherapy on Endocrine Function and Gut Microbiota in Cervical Cancer Patients Undergoing Ovarian Transposition. Int J Womens Health 2024; 16:2319-2331. [PMID: 39742347 PMCID: PMC11687098 DOI: 10.2147/ijwh.s494268] [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: 09/02/2024] [Accepted: 12/18/2024] [Indexed: 01/03/2025] Open
Abstract
Objective This study aims to investigate the effects of radiotherapy on ovarian function, endocrine function, and gut microbiota in cervical cancer patients who underwent ovarian transposition, compared to those who did not. Methods This study included 100 cervical cancer patients treated from January to June 2024, divided into a control group (50 cases, radical surgery and radiotherapy) and an observation group (50 cases, ovarian transposition surgery plus radiotherapy). Radiotherapy protocols included conventional, intensity-modulated, or conformal radiotherapy, with 6MVX rays delivering 100-200 cGy per session, 5 sessions per week for 6 weeks. In the observation group, the ovarian region was shielded with a lead plate. Outcomes measured included ovarian and endocrine function, quality of life, adverse reactions, and gut microbiota composition. DNA was extracted from fecal samples for 16S rRNA sequencing and bioinformatics analysis, including α- and β-diversity, taxonomic composition, and LEfSe analysis. Results Before radiotherapy, no significant differences in serum sex hormone levels were observed between the groups. After radiotherapy, the control group showed greater increases in FSH and LH and a more pronounced decrease in estradiol (E2) levels. Ovarian function preservation was significantly higher in the observation group (28.00% vs 0.00%). The observation group also had a higher Kupperman score 6 months post-surgery (28.01±10.22 vs 21.91±7.38). Adverse reaction rates were comparable. Gut microbiota analysis revealed differences in taxonomic composition, with higher Firmicutes (66.5% vs 65.56%) and Faecalibacterium (7.0% vs 2.7%) in the observation group, while Proteobacteria (4.1% vs 13.9%) and Shigella (2.7% vs 8.5%) were more abundant in the control group. LEfSe analysis identified notable species differences, including higher Peptoniphilus and Actinomyces in the observation group. Conclusion Ovarian transposition surgery effectively preserves ovarian function in cervical cancer patients. Changes in gut microbiota during radiotherapy may influence endocrine outcomes, warranting further research.
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Affiliation(s)
- Shuangshuang Xie
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, People’s Republic of China
| | - Miaomiao Liu
- Hengshui Maternal and Child Health Hospital Internal Medicine, Hengshui, People’s Republic of China
| | - Wei Li
- Emergency Room, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang, People’s Republic of China
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Che Mohd Nassir CMN, Che Ramli MD, Mohamad Ghazali M, Jaffer U, Abdul Hamid H, Mehat MZ, Hein ZM. The Microbiota-Gut-Brain Axis: Key Mechanisms Driving Glymphopathy and Cerebral Small Vessel Disease. Life (Basel) 2024; 15:3. [PMID: 39859943 PMCID: PMC11766513 DOI: 10.3390/life15010003] [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: 11/01/2024] [Revised: 12/19/2024] [Accepted: 12/22/2024] [Indexed: 01/27/2025] Open
Abstract
The human microbiota constitute a very complex ecosystem of microorganisms inhabiting both the inside and outside of our bodies, in which health maintenance and disease modification are the main regulatory features. The recent explosion of microbiome research has begun to detail its important role in neurological health, particularly concerning cerebral small vessel disease (CSVD), a disorder associated with cognitive decline and vascular dementia. This narrative review represents state-of-the-art knowledge of the intimate, complex interplay between microbiota and brain health through the gut-brain axis (GBA) and the emerging role of glymphatic system dysfunction (glymphopathy) and circulating cell-derived microparticles (MPs) as mediators of these interactions. We discuss how microbial dysbiosis promotes neuroinflammation, vascular dysfunction, and impaired waste clearance in the brain, which are critical factors in the pathogenesis of CSVD. Further, we discuss lifestyle factors that shape the composition and functionality of the microbiota, focusing on sleep as a modifiable risk factor in neurological disorders. This narrative review presents recent microbiome research from a neuroscientific and vascular perspective to establish future therapeutic avenues in targeting the microbiota to improve brain health and reduce the burden of CSVD.
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Affiliation(s)
- Che Mohd Nasril Che Mohd Nassir
- Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia; (C.M.N.C.M.N.); (M.M.G.)
| | - Muhammad Danial Che Ramli
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam 40150, Selangor, Malaysia;
| | - Mazira Mohamad Ghazali
- Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia; (C.M.N.C.M.N.); (M.M.G.)
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Usman Jaffer
- Kulliyyah of Islamic Revealed Knowledge and Human Sciences, International Islamic University Malaysia, Kuala Lumpur 50728, Malaysia;
| | - Hafizah Abdul Hamid
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (H.A.H.); (M.Z.M.)
| | - Muhammad Zulfadli Mehat
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (H.A.H.); (M.Z.M.)
| | - Zaw Myo Hein
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates
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30
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Cotoia A, Charitos IA, Corriero A, Tamburrano S, Cinnella G. The Role of Macronutrients and Gut Microbiota in Neuroinflammation Post-Traumatic Brain Injury: A Narrative Review. Nutrients 2024; 16:4359. [PMID: 39770985 PMCID: PMC11677121 DOI: 10.3390/nu16244359] [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: 11/05/2024] [Revised: 12/07/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Traumatic brain injury (TBI) represents a multifaceted pathological condition resulting from external forces that disrupt neuronal integrity and function. This narrative review explores the intricate relationship between dietary macronutrients, gut microbiota (GM), and neuroinflammation in the TBI. We delineate the dual aspects of TBI: the immediate mechanical damage (primary injury) and the subsequent biological processes (secondary injury) that exacerbate neuronal damage. Dysregulation of the gut-brain axis emerges as a critical factor in the neuroinflammatory response, emphasizing the role of the GM in mediating immune responses. Recent evidence indicates that specific macronutrients, including lipids, proteins, and probiotics, can influence microbiota composition and in turn modulate neuroinflammation. Moreover, specialized dietary interventions may promote resilience against secondary insults and support neurological recovery post-TBI. This review aims to synthesize the current preclinical and clinical evidence on the potential of dietary strategies in mitigating neuroinflammatory pathways, suggesting that targeted nutrition and gut health optimization could serve as promising therapeutic modalities in TBI management.
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Affiliation(s)
- Antonella Cotoia
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
| | - Ioannis Alexandros Charitos
- Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, “Istitute” of Bari, 70124 Bari, Italy;
- Doctoral School on Applied Neurosciences, Dipartimento di Biomedicina Traslazionale e Neuroscienze (DiBraiN), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Alberto Corriero
- Department of Interdisciplinary Medicine-ICU Section, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Stefania Tamburrano
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
| | - Gilda Cinnella
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
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31
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Jászberényi M, Thurzó B, Jayakumar AR, Schally AV. The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease. Int J Mol Sci 2024; 25:13086. [PMID: 39684795 DOI: 10.3390/ijms252313086] [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: 10/12/2024] [Revised: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
Alzheimer's disease imposes an increasing burden on aging Western societies. The disorder most frequently appears in its sporadic form, which can be caused by environmental and polygenic factors or monogenic conditions of incomplete penetrance. According to the authors, in the majority of cases, Alzheimer's disease represents an aggravated form of the natural aging of the central nervous system. It can be characterized by the decreased elimination of amyloid β1-42 and the concomitant accumulation of degradation-resistant amyloid plaques. In the present paper, the dysfunction of neuropeptide regulators, which contributes to the pathophysiologic acceleration of senile dementia, is reviewed. However, in the present review, exclusively those neuropeptides or neuropeptide families are scrutinized, and the authors' investigations into their physiologic and pathophysiologic activities have made significant contributions to the literature. Therefore, the pathophysiologic role of orexins, neuromedins, RFamides, corticotrope-releasing hormone family, growth hormone-releasing hormone, gonadotropin-releasing hormone, ghrelin, apelin, and natriuretic peptides are discussed in detail. Finally, the therapeutic potential of neuropeptide antagonists and agonists in the inhibition of disease progression is discussed here.
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Affiliation(s)
- Miklós Jászberényi
- Department of Pathophysiology, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary
| | - Balázs Thurzó
- Department of Pathophysiology, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary
- Emergency Patient Care Unit, Albert Szent-Györgyi Health Centre, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
| | - Arumugam R Jayakumar
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Andrew V Schally
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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32
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Sugden SG, Merlo G. Using lifestyle interventions and the gut microbiota to improve PTSD symptoms. Front Neurosci 2024; 18:1488841. [PMID: 39691626 PMCID: PMC11649671 DOI: 10.3389/fnins.2024.1488841] [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: 08/30/2024] [Accepted: 11/04/2024] [Indexed: 12/19/2024] Open
Abstract
Posttraumatic stress disorder is part of a spectrum of psychological symptoms that are frequently linked with a single defining traumatic experience. Symptoms can vary over the lifespan in intensity based on additional life stressors, individual stability, and connectedness to purpose. Historically, treatment has centered on psychotropic agents and individual and group therapy to increase the individual's window of tolerance, improve emotional dysregulation, and strengthen relationships. Unfortunately, there is a growing segment of individuals with posttraumatic stress disorder who do not respond to these traditional treatments, perhaps because they do not address the multidirectional relationships between chronic cortisol, changes in the brain gut microbiota system, neuroinflammation, and posttraumatic symptoms. We will review the literature and explain how trauma impacts the neuroendocrine and neuroimmunology within the brain, how these processes influence the brain gut microbiota system, and provide a mechanism for the development of posttraumatic stress disorder symptoms. Finally, we will show how the lifestyle psychiatry model provides symptom amelioration.
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Affiliation(s)
- Steven G. Sugden
- Department of Psychiatry, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, United States
| | - Gia Merlo
- Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, United States
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Rout M, Kar DM, Dubey D, Kispotta S, Sarangi P, Prusty SK. Neuroprotective effect of Bacillus subtilis in haloperidol induced rat model, targeting the microbiota-gut-brain axis. J Mol Histol 2024; 56:18. [PMID: 39625518 DOI: 10.1007/s10735-024-10307-0] [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: 05/22/2024] [Accepted: 10/04/2024] [Indexed: 02/07/2025]
Abstract
Functional microbes regulate Parkinson's disease (PD), according to contemporary research. The mechanism by which probiotics (PBT) improve PD was not fully explored yet. We examined the antioxidant impact and mechanism of PBT (Bacillus subtilis) on PD using gut-brain axis regulation. To establish a model of PD, rats were given haloperidol (HAL) intraperitoneally (i.p.) in this study. The standard group received L-DOPA for 21 days. After that, the motor function was assessed using different neurobehavioral tests. Further estimation comprehends the build up of alpha-synuclein, the manifestation of monoamine oxidase-B (MAO-B) activity, the deterioration of dopaminergic neurons and the induction of an oxidative stress reaction. In addition, the concentration of intestinal microbes was measured. These findings demonstrated that the administration of PBT in combination with L-dopa could alleviate motor impairments caused by HAL, the deterioration of dopaminergic neurons, and the build up of α-synuclein. Furthermore, the levels of superoxide dismutase (SOD) and dopamine were considerably raised by co-administration of L-dopa and PBT in the case of HAL-treated rats, whereas the levels of alpha-synuclein, MAO-B, and malondialdehyde (MDA) were reduced. Particularly, PBT administration reduced the gut microbial dysbiosis, which in turn raised the concentration of good bacteria i.e., Bifidobacterium and reduced the concentration of E. coli in experimental animals. These findings indicated that PBT might represent a promising candidate to inhibit the progression of Parkinson's disease by targeting the gut-brain axis.
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Affiliation(s)
- Monalisa Rout
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India
| | - Durga Madhab Kar
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India
| | - Debasmita Dubey
- Institute of Medical Sciences and Sum Hospital, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India
| | - Sneha Kispotta
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India
| | - Prerna Sarangi
- Centre for Biotechnology, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India
| | - Shakti Ketan Prusty
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan deemed to Be University, Bhubaneswar, India.
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Mormede E, Mormede P. Genetic Variation of Hypothalamic-Pituitary-Adrenal Axis Activity in Farm Animals and Beyond. Neuroendocrinology 2024; 115:128-137. [PMID: 39626641 DOI: 10.1159/000542831] [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: 04/11/2024] [Accepted: 11/14/2024] [Indexed: 01/21/2025]
Abstract
BACKGROUND Many experimental data in several species clearly demonstrate the important genetic contribution to variations in HPA axis activity. The influence of corticosteroid hormones on adaptive processes and on production traits such as growth rate, feed efficiency, carcass composition, and meat quality is a strong impetus to the search for the molecular bases of these differences for efficient genetic selection. SUMMARY Three main sources of genetic variability have been documented so far in farm animal species, the adrenal cortex sensitivity to ACTH-regulating corticosteroid hormone production, the bioavailability of corticosteroid hormones and especially corticosteroid-binding globulin capacity, and glucocorticoid receptor function. The effect of single mutations may be dependent on the genetic background, and genetic variation of cortisol levels may have different functional consequences depending on the molecular mechanisms responsible for this change. KEY MESSAGES Understanding the genetic basis of HPA axis activity allows the development of genomic tools and breeding technologies aimed at improving adaptive capacity and stress tolerance in farm animals and their use as valuable models for the genetic study of the HPA axis and the correlation with adaptation, metabolism, and other functions regulated by adrenal hormones, and associated pathologies (obesity, cardiovascular, etc.). The next step will be to explore HPA axis variability from a system genetics perspective including the multiple sources of variation and their interactions. This multifactorial approach is a prerequisite to the use of the HPA axis phenotypes in the genetic selection for more productive and robust animals, with a high level of production of quality products.
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Affiliation(s)
- Elena Mormede
- GenPhySE, Université de Toulouse, INRAE, INPT, ENVT, Toulouse, France
| | - Pierre Mormede
- GenPhySE, Université de Toulouse, INRAE, INPT, ENVT, Toulouse, France
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35
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S S, L.S. D, Rajendran P, N H, Singh S A. Exploring the potential of probiotics in Alzheimer's disease and gut dysbiosis. IBRO Neurosci Rep 2024; 17:441-455. [PMID: 39629018 PMCID: PMC11612366 DOI: 10.1016/j.ibneur.2024.11.004] [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: 09/15/2024] [Revised: 11/04/2024] [Accepted: 11/05/2024] [Indexed: 12/06/2024] Open
Abstract
Alzheimer's disease is a fatal neurodegenerative disorder that causes memory loss and cognitive decline in older people. There is increasing evidence suggesting that gut microbiota alteration is a cause of Alzheimer's disease pathogenesis. This review explores the link between gut dysbiosis and the development of Alzheimer's disease contributing to neuroinflammation, amyloid β accumulation, and cognitive decline. We examine the recent studies that illustrate the gut-brain axis (GBA) as a bidirectional communication between the gut and brain and how its alteration can influence neurological health. Furthermore, we discuss the potential of probiotic supplementation as a management approach to restore gut microbiota balance, and ultimately improve cognitive function in AD patients. Based on current research findings, this review aims to provide insights into the promising role of probiotics in Alzheimer's disease management and the need for further investigation into microbiota-targeted interventions.
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Affiliation(s)
- Sowmiya S
- Department of Pharmacology, Dr M.G.R. Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai, Tamil Nadu 600 077, India
| | - Dhivya L.S.
- Department of Pharmaceutical Chemistry, Dr M.G.R. Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai, Tamil Nadu 600 077, India
| | - Praveen Rajendran
- Department of Pharmacology, Dr M.G.R. Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai, Tamil Nadu 600 077, India
| | - Harikrishnan N
- Department of pharmaceutical analysis, Dr M.G.R. Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai, Tamil Nadu 600 077, India
| | - Ankul Singh S
- Department of Pharmacology, Dr M.G.R. Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai, Tamil Nadu 600 077, India
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Kirkik D, Kalkanli Tas S. Unveiling the intricacies of irritable bowel syndrome. World J Gastroenterol 2024; 30:4763-4767. [PMID: 39610774 PMCID: PMC11580607 DOI: 10.3748/wjg.v30.i44.4763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 09/26/2024] [Accepted: 10/18/2024] [Indexed: 11/12/2024] Open
Abstract
Irritable bowel syndrome (IBS) remains a challenging condition both for patients and clinicians, characterized by its chronic nature and the elusive complexity of its underlying mechanisms. The multifaceted relationship between the neuroendocrine axis, gut microbiota, and inflammatory response has emerged as a focal point in recent research, offering new insights into the pathophysiology of IBS. The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut, often referred to as the "gut-brain axis". This bidirectional communication is essential for regulating gastrointestinal function, stress responses, and overall homeostasis. Dysregulation of this axis, as highlighted by elevated cortisol and serotonin levels in IBS patients, suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms. These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS, potentially guiding more effective, personalized treatment approaches. Equally important is the role of the gut microbiota, a diverse and dynamic ecosystem that directly impacts gut health. This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses. These findings align with the growing recognition that gut microbiota is a critical player in IBS, influencing both the disease's onset and progression.
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Affiliation(s)
- Duygu Kirkik
- Department of Immunology, University of Health Sciences, Hamidiye Medicine Faculty, Istanbul 34668, Türkiye
- Department of Medical Biology, University of Health Sciences, Hamidiye Medicine Faculty, Istanbul 34668, Türkiye
| | - Sevgi Kalkanli Tas
- Department of Immunology, University of Health Sciences, Hamidiye Medicine Faculty, Istanbul 34668, Türkiye
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Abildinova GZ, Benberin VV, Vochshenkova TA, Afshar A, Mussin NM, Kaliyev AA, Zhussupova Z, Tamadon A. The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function. Front Microbiol 2024; 15:1463958. [PMID: 39659426 PMCID: PMC11628546 DOI: 10.3389/fmicb.2024.1463958] [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: 07/12/2024] [Accepted: 11/13/2024] [Indexed: 12/12/2024] Open
Abstract
The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.
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Affiliation(s)
- Gulshara Zh Abildinova
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Valeriy V. Benberin
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Tamara A. Vochshenkova
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Alireza Afshar
- Gerontology Center, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
- Corporate Fund “Institute for Innovational and Profilaxy Medicine”, Astana, Kazakhstan
| | - Nadiar M. Mussin
- Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan
| | - Asset A. Kaliyev
- Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan
| | - Zhanna Zhussupova
- Department of Neurology, Psychiatry and Narcology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Amin Tamadon
- Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- PerciaVista R&D Co., Shiraz, Iran
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Dezfouli MA, Rashidi SK, Yazdanfar N, Khalili H, Goudarzi M, Saadi A, Kiani Deh Kiani A. The emerging roles of neuroactive components produced by gut microbiota. Mol Biol Rep 2024; 52:1. [PMID: 39570444 DOI: 10.1007/s11033-024-10097-4] [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: 07/07/2024] [Accepted: 11/06/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND As a multifunctional ecosystem, the human digestive system contains a complex network of microorganisms, collectively known as gut microbiota. This consortium composed of more than 1013 microorganisms and Firmicutes and Bacteroidetes are the dominant microbes. Gut microbiota is increasingly recognized for its critical role in physiological processes beyond digestion. Gut microbiota participates in a symbiotic relationship with the host and takes advantage of intestinal nutrients and mutually participates in the digestion of complex carbohydrates and maintaining intestinal functions. METHOD AND RESULT We reviewed the neuroactive components produced by gut microbiota. Interestingly, microbiota plays a crucial role in regulating the activity of the intestinal lymphatic system, regulation of the intestinal epithelial barrier, and maintaining the tolerance to food immunostimulating molecules. The gut-brain axis is a two-way communication pathway that links the gut microbiota to the central nervous system (CNS) and importantly is involved in neurodevelopment, cognition, emotion and synaptic transmissions. The connections between gut microbiota and CNS are via endocrine system, immune system and vagus nerve. CONCLUSION The gut microbiota produces common neurotransmitters and neuromodulators of the nervous system. These compounds play a role in neuronal functions, immune system regulation, gastrointestinal homeostasis, permeability of the blood brain barrier and other physiological processes. This review investigates the essential aspects of the neurotransmitters and neuromodulators produced by gut microbiota and their implications in health and disease.
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Affiliation(s)
- Mitra Ansari Dezfouli
- Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Seyed Khalil Rashidi
- Department of Medical Biotechnology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nada Yazdanfar
- Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hamidreza Khalili
- Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehdi Goudarzi
- Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Saadi
- Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Kiani Deh Kiani
- Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Magistrelli L, Contaldi E, Visciglia A, Deusebio G, Pane M, Amoruso A. The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson's Disease: Preliminary In Vivo Data. Brain Sci 2024; 14:1147. [PMID: 39595910 PMCID: PMC11592242 DOI: 10.3390/brainsci14111147] [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: 10/30/2024] [Revised: 11/11/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024] Open
Abstract
Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson's disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-α, IFN-γ, IL-6, and TGF-β) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 ± 4.08 vs. 12.74 ± 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 ± 21.41 vs. 30.11 ± 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 ± 4.14 vs. 1.89 ± 2.54, p = 0.021). A reduction of IFN-γ levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-β. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs.
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Affiliation(s)
- Luca Magistrelli
- Parkinson Institute Milan, ASST G.Pini-CTO, Via Bignami 1, 20126 Milan, Italy;
| | - Elena Contaldi
- Parkinson Institute Milan, ASST G.Pini-CTO, Via Bignami 1, 20126 Milan, Italy;
| | - Annalisa Visciglia
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Giovanni Deusebio
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Marco Pane
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Angela Amoruso
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
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Castro CM, Mithal A, Deyhim T, Rabinowitz LG, Olagoke O, Freedman SD, Cheifetz AS, Ballou SK, Papamichael K. Morning Salivary Cortisol Has a Positive Correlation with GAD-7 Scores in Patients with Ulcerative Colitis. J Clin Med 2024; 13:6707. [PMID: 39597852 PMCID: PMC11595166 DOI: 10.3390/jcm13226707] [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: 10/13/2024] [Revised: 10/30/2024] [Accepted: 11/06/2024] [Indexed: 11/29/2024] Open
Abstract
Objectives: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Earlier onset of IBD symptoms has been linked to a higher prevalence of depression and anxiety. Evidence supports that cortisol abnormalities correlate with the development and severity of autoimmune diseases. The primary aim of this study was to investigate the correlation of morning salivary cortisol levels with self-reported mood (depression and anxiety) and quality of life in patients with IBD. Methods: This was a prospective, single-center study including outpatients with IBD. Enrolled patients provided a one-time morning salivary cortisol sample and electronically completed a one-time survey encompassing self-reported quality of life (Short Inflammatory Bowel Disease Questionnaire (SIBDQ)) and mood (Patient Health Questionnaire 8 (PHQ-8), General Anxiety Disorder-7 (GAD-7)). Results: A total of 36 patients (UC, n = 21) were included in the study. There was no correlation between morning salivary cortisol and depressive symptoms (PHQ-8: r = 0.007, p = 0.968) or quality of life (SIBDQ: r = -0.095, p = 0.606). However, there was a trend towards a positive correlation between self-reported anxiety symptoms by GAD-7 and salivary cortisol (r = 0.347, p = 0.052). A subgroup analysis showed a positive correlation between morning salivary cortisol and GAD-7 scores in patients with UC (r = 0.535, p = 0.015), but not in patients with CD (r = 0.064, p = 0.843). Conclusions: This pilot study is the first to associate cortisol with anxiety symptom severity in UC. Further research is needed to investigate the link between salivary cortisol, neuropsychiatric disease, and IBD outcomes.
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Affiliation(s)
- Cristina M. Castro
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (C.M.C.); (A.M.)
| | - Aditya Mithal
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (C.M.C.); (A.M.)
| | - Tina Deyhim
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Loren G. Rabinowitz
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Olawande Olagoke
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Steven D. Freedman
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Adam S. Cheifetz
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Sarah K. Ballou
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
| | - Konstantinos Papamichael
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (T.D.); (L.G.R.); (O.O.); (S.D.F.); (A.S.C.); (S.K.B.)
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Abeltino A, Hatem D, Serantoni C, Riente A, De Giulio MM, De Spirito M, De Maio F, Maulucci G. Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine. Nutrients 2024; 16:3806. [PMID: 39599593 PMCID: PMC11597134 DOI: 10.3390/nu16223806] [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: 10/08/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024] Open
Abstract
Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota-host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota-host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary-microbiota-host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.
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Affiliation(s)
- Alessio Abeltino
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Duaa Hatem
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Cassandra Serantoni
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Alessia Riente
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Michele Maria De Giulio
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Marco De Spirito
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Flavio De Maio
- Department of Laboratory and Infectious Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Giuseppe Maulucci
- Metabolic Intelligence Lab, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy; (A.A.); (D.H.); (C.S.); (A.R.); (M.M.D.G.); (M.D.S.)
- UOC Physics for Life Sciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
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Bano N, Khan S, Ahamad S, Kanshana JS, Dar NJ, Khan S, Nazir A, Bhat SA. Microglia and gut microbiota: A double-edged sword in Alzheimer's disease. Ageing Res Rev 2024; 101:102515. [PMID: 39321881 DOI: 10.1016/j.arr.2024.102515] [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: 04/23/2024] [Revised: 09/06/2024] [Accepted: 09/19/2024] [Indexed: 09/27/2024]
Abstract
The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.
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Affiliation(s)
- Nargis Bano
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Sameera Khan
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Shakir Ahamad
- Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
| | - Jitendra Singh Kanshana
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburg, PA, USA.
| | - Nawab John Dar
- CNB, SALK Institute of Biological Sciences, La Jolla, CA 92037, USA.
| | - Sumbul Khan
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Aamir Nazir
- Division of Neuroscience and Ageing Biology, CSIR-Central Drug Research Institute, Lucknow, UP, India; Academy of Scientific and Innovative Research, New Delhi, India.
| | - Shahnawaz Ali Bhat
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
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Feng Y, Hao F. Advances in natural polysaccharides in Alzheimer's disease and Parkinson's disease: Insights from the brain-gut axis. Trends Food Sci Technol 2024; 153:104678. [DOI: 10.1016/j.tifs.2024.104678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Nie D, Wang D, Wang Z, Fang Q, Wang H, Xie W, Li C, Zhang Y. The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice. MICROBIOME 2024; 12:225. [PMID: 39482760 PMCID: PMC11529176 DOI: 10.1186/s40168-024-01939-1] [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: 03/28/2024] [Accepted: 09/23/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology. RESULTS The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety. CONCLUSIONS In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.
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Affiliation(s)
- Ding Nie
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Dawei Wang
- Department of Neurosurgery, Air Force Medical University Tangdu Hospital, Xi'an, China
| | - Zhenhua Wang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Qiuyue Fang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Hongyun Wang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Weiyan Xie
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
| | - Chuzhong Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
| | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
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Liu YE, Zhao Z, He H, Li L, Xiao C, Zhou T, You Z, Zhang J. Stress-induced obesity in mice causes cognitive decline associated with inhibition of hippocampal neurogenesis and dysfunctional gut microbiota. Front Microbiol 2024; 15:1381423. [PMID: 39539712 PMCID: PMC11557545 DOI: 10.3389/fmicb.2024.1381423] [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: 02/03/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
Effects of stress on obesity have been thoroughly studied in high-fat diet fed mice, but not in normal diet fed mice, which is important to clarify because even on a normal diet, some individuals will become obese under stress conditions. Here we compared mice that showed substantial weight gain or loss under chronic mild stress while on a normal diet; we compared the two groups in terms of cognitive function, hypothalamic-pituitary-adrenal signaling, neurogenesis and activation of microglia in hippocampus, gene expression and composition of the gut microbiome. Chronic mild stress induced diet-independent obesity in approximately 20% of animals, and it involved inflammatory responses in peripheral and central nervous system as well as hyperactivation of the hypothalamic-pituitary-adrenal signaling and of microglia in the hippocampus, which were associated with cognitive deficits and impaired hippocampal neurogenesis. It significantly increased in relative abundance at the phylum level (Firmicutes), at the family level (Prevotellaceae ucg - 001 and Lachnospiraceae NK4a136), at the genus level (Dubosiella and Turicibacter) for some enteric flora, while reducing the relative abundance at the family level (Lactobacillaceae and Erysipelotrichaceae), at the genus level (Bacteroidota, Alistipes, Alloprevotella, Bifidobacterium and Desulfovibrio) for some enteric flora. These results suggest that stress, independently of diet, can induce obesity and cognitive decline that involve dysfunctional gut microbiota. These insights imply that mitigation of hypothalamic-pituitary-adrenal signaling and microglial activation as well as remodeling of gut microbiota may reverse stress-induced obesity and associated cognitive decline.
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Affiliation(s)
- Yu-e Liu
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Zhihuang Zhao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Haili He
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Liangyuan Li
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Chenghong Xiao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Tao Zhou
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Zili You
- The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jinqiang Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
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Varghese S, Rao S, Khattak A, Zamir F, Chaari A. Physical Exercise and the Gut Microbiome: A Bidirectional Relationship Influencing Health and Performance. Nutrients 2024; 16:3663. [PMID: 39519496 PMCID: PMC11547208 DOI: 10.3390/nu16213663] [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: 09/17/2024] [Revised: 10/18/2024] [Accepted: 10/19/2024] [Indexed: 11/16/2024] Open
Abstract
Background/Objectives: The human gut microbiome is a complex ecosystem of microorganisms that can influence our health and exercise habits. On the other hand, physical exercise can also impact our microbiome, affecting our health. Our narrative review examines the bidirectional relationship between physical activity and the gut microbiome, as well as the potential for targeted probiotic regimens to enhance sports performance. Methods: We conducted a comprehensive literature review to select articles published up till January 2024 on the topics of physical exercise, sports, probiotics, and gut microbiota from major scientific databases, incorporating over 100 studies. Results: We found that the impact of physical activity on the gut microbiome varies with the type and intensity of exercise. Moderate exercise promotes a healthy immune system, while high-intensity exercise for a long duration can cause a leaky gut and consequent systemic inflammation, which may disrupt the microbial balance. Combining aerobic and resistance training significantly affects bacterial diversity, linked to a lower prevalence of chronic metabolic disorders. Furthermore, exercise enhances gut microbiome diversity, increases SCFA production, improves nutrient utilization, and modulates neural and hormonal pathways, improving gut barrier integrity. Our findings also showed probiotic supplementation is associated with decreased inflammation, enhanced sports performance, and fewer gastrointestinal disturbances, suggesting that the relationship between the gut microbiome and physical activity is mutually influential. Conclusions: The bidirectional relationship between physical activity and the gut microbiome is exemplified by how exercise can promote beneficial bacteria while a healthy gut microbiome can potentially enhance exercise ability through various mechanisms. These findings underscore the importance of adding potential tailored exercise regimens and probiotic supplementation that consider individual microbiome profiles into exercise programs.
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Affiliation(s)
| | | | | | | | - Ali Chaari
- Department of Biochemistry, Premedical Division, Weill Cornell Medicine–Qatar, Qatar Foundation, Education City, Doha P.O. Box 24144, Qatar; (S.V.); (S.R.); (A.K.); (F.Z.)
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Jain M, Anand A, Sharma N, Shamim MA, Enioutina EY. Effect of Probiotics Supplementation on Cortisol Levels: A Systematic Review and Meta-Analysis. Nutrients 2024; 16:3564. [PMID: 39458560 PMCID: PMC11510182 DOI: 10.3390/nu16203564] [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: 08/31/2024] [Revised: 09/25/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Several randomized controlled trials (RCTs) have shown conflicting results on cortisol levels following probiotic administration in healthy and diseased populations. Previous analyses were inconclusive due to limited studies, and evidence is lacking on how these effects vary by health status; region; therapy duration; medications, and use of single or multiple strains. Methods: In this systematic review and meta-analysis (PROSPERO [CRD42024538539]), we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, CINAHL, ProQuest, and Web of Science Preprints until 13 August 2024, for RCTs on probiotic administration, either alone or combined, across all age groups and without specific medical condition requirements. We applied random-effects meta-analysis, assessed bias using the Cochrane RoB 2 tool, and evaluated evidence certainty with GRADE. Findings: We screened 1739 records and retrieved 46 RCTs (3516 participants). Probiotics supplementation decreased cortisol levels compared to the control arm [46 RCTs; SMD: -0.45; 95% CI: -0.83; -0.07; I2: 92.5%, low certainty]. Among various subgroups; probiotics supplementation decreased the cortisol levels in the subgroups without concomitant medications [37 RCTs; SMD: -0.30; 95% CI [-0.58; -0.03], I2: 88.7%] with a single probiotic strain [30 RCTs; SMD: -0.33; 95% CI: -0.63; -0.028; I2: 88.8%], in a healthy population [35 RCTs; SMD:-0.3; 95% CI: -0.58; -0.03; I2: 88.7] and in the Asia region [21 RCTs; SMD: -0.83; 95% CI: -1.58; -0.07; I2: 95%]. Interpretation: A low level of evidence suggests probiotics might reduce cortisol levels, but more targeted studies are needed to identify variables affecting the response in specific subgroups.
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Affiliation(s)
- Manav Jain
- Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT 84108, USA;
| | - Aishwarya Anand
- Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Nisha Sharma
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India;
| | - Muhammad Aaqib Shamim
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur 342005, India;
| | - Elena Y. Enioutina
- Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT 84108, USA;
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Silva JF, de Souza WM, Mello JDC, Ceccato HD, Oliveira PDSP, Ayrizono MDLS, Leal RF. Evidence linking gut-brain axis and Crohn's disease, focusing on neurotrophic dysfunctions and radiological imaging analysis - a systematic review. Am J Transl Res 2024; 16:6029-6040. [PMID: 39544780 PMCID: PMC11558361 DOI: 10.62347/owyy4960] [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: 06/20/2024] [Accepted: 09/22/2024] [Indexed: 11/17/2024]
Abstract
OBJECTIVE To conduct a systematic review (SR) to find evidence for a connection between Crohn's disease (CD) and the gut-brain axis (GBA). METHODS This study conducted a systematic review (SR) employing a search strategy and strict inclusion criteria. It was conducted by searching for studies published between 2017 and 2024 in the following databases: PUBMED, PUBMED PMC, BVS-BIREME, SCOPUS, WEB OF SCIENCE, EMBASE, and COCHRANE. RESULTS Fifty original research articles were included. Among these, 20 studies addressed neuroimaging methods to evaluate CD patients' functional or structural brain changes. Neurodegenerative diseases were the second most addressed topic in the studies, with 18 articles related to different diseases such as Parkinson's disease, Alzheimer's disease, dementia, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Multiple System Atrophy. Eight articles addressed sleep disorders related to CD; two explored Electroencephalography changes; one investigated Brain-Derived Neurotrophic Factor serum levels and one correlated vagotomy with CD. CONCLUSION Interest in the link between CD and GBA is increasing, but studies remain varied and inconclusive, spanning from epidemiology to brain imaging and neglecting to investigate a mechanistic relationship. This SR underscores the need for further research to better understand the potential role of GBA in the prognosis and etiology of CD, highlighting its complexity.
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Affiliation(s)
- Julian Furtado Silva
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - William Moraes de Souza
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - Juliana Delgado Campos Mello
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - Hugo Dugolin Ceccato
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - Priscilla de Sene Portel Oliveira
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP) Campinas, São Paulo, Brazil
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49
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Kang HJ, Kim SW, Kim SM, La TM, Hyun JE, Lee SW, Kim JH. Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis. Animals (Basel) 2024; 14:2883. [PMID: 39409832 PMCID: PMC11476382 DOI: 10.3390/ani14192883] [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: 08/26/2024] [Revised: 09/24/2024] [Accepted: 09/30/2024] [Indexed: 10/20/2024] Open
Abstract
Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.
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Affiliation(s)
- Hee-Jun Kang
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (H.-J.K.); (S.-W.K.); (J.-E.H.)
| | - Sang-Won Kim
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (H.-J.K.); (S.-W.K.); (J.-E.H.)
| | - Seon-Myung Kim
- KR Lab Bio Incorporation, Suwon 16429, Republic of Korea;
| | - Tae-Min La
- Department of Veterinary Microbiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (T.-M.L.); (S.-W.L.)
| | - Jae-Eun Hyun
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (H.-J.K.); (S.-W.K.); (J.-E.H.)
| | - Sang-Won Lee
- Department of Veterinary Microbiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (T.-M.L.); (S.-W.L.)
| | - Jung-Hyun Kim
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; (H.-J.K.); (S.-W.K.); (J.-E.H.)
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50
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Yang W, Cui H, Wang C, Wang X, Yan C, Cheng W. A review of the pathogenesis of epilepsy based on the microbiota-gut-brain-axis theory. Front Mol Neurosci 2024; 17:1454780. [PMID: 39421261 PMCID: PMC11484502 DOI: 10.3389/fnmol.2024.1454780] [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: 06/25/2024] [Accepted: 09/20/2024] [Indexed: 10/19/2024] Open
Abstract
The pathogenesis of epilepsy is related to the microbiota-gut-brain axis, but the mechanism has not been clarified. The microbiota-gut-brain axis is divided into the microbiota-gut-brain axis (upward pathways) and the brain-gut-microbiota axis (downward pathways) according to the direction of conduction. Gut microorganisms are involved in pathological and physiological processes in the human body and participate in epileptogenesis through neurological, immunological, endocrine, and metabolic pathways, as well as through the gut barrier and blood brain barrier mediated upward pathways. After epilepsy, the downward pathway mediated by the HPA axis and autonomic nerves triggers "leaky brain "and "leaky gut," resulting in the formation of microbial structures and enterobacterial metabolites associated with epileptogenicity, re-initiating seizures via the upward pathway. Characteristic changes in microbial and metabolic pathways in the gut of epileptic patients provide new targets for clinical prevention and treatment of epilepsy through the upward pathway. Based on these changes, this review further redescribes the pathogenesis of epilepsy and provides a new direction for its prevention and treatment.
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Affiliation(s)
- Wentao Yang
- Department of Fist Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hua Cui
- Department of Fist Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Chaojie Wang
- Department of Fist Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xuan Wang
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Ciai Yan
- Department of Fist Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Weiping Cheng
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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