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Wei Y, Zhao S, Zhao H, Bao D, Liu J, Shao H, Zhang S, Yi S, Wang K, Hu G. FoxO4 reduces the damage and mechanism of PEDV-infected IPEC-J2 cells through the NF-κB/MLCK pathway. Vet Microbiol 2025; 306:110568. [PMID: 40398348 DOI: 10.1016/j.vetmic.2025.110568] [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: 03/04/2025] [Revised: 05/13/2025] [Accepted: 05/17/2025] [Indexed: 05/23/2025]
Abstract
Porcine epidemic diarrhea (PED) incurs substantial economic losses to the pig industry. During viral infection of cells, the activity of NF-κB is upregulated. As an endogenous inhibitor, FoxO4 plays a crucial role in antagonizing NF-κB activity, inhibiting the NF-κB-mediated MLCK signaling pathway, altering the expression of cellular tight junctions (TJs) and pro-inflammatory cytokines, and protecting intestinal epithelial cells from damage. However, there are limited reports on this inhibitory and protective effect in PEDV-infected IPEC-J2 cells. Therefore, this experiment employed methods such as homologous recombination, qRT-PCR, Western blotting, co-immunoprecipitation, laser confocal microscopy, and cell transmembrane resistance assays to investigate the effect of FoxO4 on indicators related to cell damage through the NF-κB/MLCK pathway in infected cells. The results demonstrated the successful construction of FoxO4 and NF-κB factor p65 expression vectors, confirming the interaction between the two in IPEC-J2 cells. FoxO4 effectively antagonizes the expression of NF-κB/MLCK pathway factors in infected cells, and through this action, it reduces the permeability of infected cells, maintains the integrity of the cell membrane, upregulates the expression of TJ proteins, antagonizes the expression of pro-inflamma-tory factors, and exerts effects in promoting cell apoptosis and antagonizing viral replication.This study further elucidates the molecular mechanisms underlying cell damage caused by PEDV and offers new potential targets for protecting intestinal epithelial barrier function.
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Affiliation(s)
- Yiming Wei
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Shihui Zhao
- Animal Husbandry and Veterinary Science Research Institute of Jilin Province, Changchun, China.
| | - Han Zhao
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Di Bao
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Jiuyuan Liu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Hongze Shao
- Animal Husbandry and Veterinary Science Research Institute of Jilin Province, Changchun, China.
| | - Shuang Zhang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Shushuai Yi
- College of Animal Science and Technology,Jilin University of Agricultural Science and Technology, Jilin, China.
| | - Kai Wang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
| | - Guixue Hu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
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2
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Adelfio M, Callen GE, He X, Paster BJ, Hasturk H, Ghezzi CE. Engineered Tissue Models to Decode Host-Microbiota Interactions. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2417687. [PMID: 40364768 DOI: 10.1002/advs.202417687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 04/13/2025] [Indexed: 05/15/2025]
Abstract
A mutualistic co-evolution exists between the host and its associated microbiota in the human body. Bacteria establish ecological niches in various tissues of the body, locally influencing their physiology and functions, but also contributing to the well-being of the whole organism through systemic communication with other distant niches (axis). Emerging evidence indicates that when the composition of the microbiota inhabiting the niche changes toward a pathogenic state (dysbiosis) and interactions with the host become unbalanced, diseases may present. In addition, imbalances within a single niche can cause dysbiosis in distant organs. Current research efforts are focused on elucidating the mechanisms leading to dysbiosis, with the goal of restoring tissue homeostasis. In vitro models can provide critical experimental platforms to address this need, by reproducing the niche cyto-architecture and physiology with high fidelity. This review surveys current in in vitro host-microbiota research strategies and provides a roadmap that can guide the field in further developing physiologically relevant in vitro models of ecological niches, thus enabling investigation of the role of the microbiota in human health and diseases. Lastly, given the Food and Drug Administration Modernization Act 2.0, this review highlights emerging in vitro strategies to support the development and validation of new therapies on the market.
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Affiliation(s)
- Miryam Adelfio
- Department of Biomedical Engineering, University of Massachusetts-Lowell, Lowell, MA, 01854, USA
| | - Grace E Callen
- Department of Biomedical Engineering, University of Massachusetts-Lowell, Lowell, MA, 01854, USA
| | - Xuesong He
- ADA Forsyth Institute, 245 First St, Cambridge, MA, 02142, USA
| | - Bruce J Paster
- ADA Forsyth Institute, 245 First St, Cambridge, MA, 02142, USA
| | - Hatice Hasturk
- ADA Forsyth Institute, 245 First St, Cambridge, MA, 02142, USA
| | - Chiara E Ghezzi
- Department of Biomedical Engineering, University of Massachusetts-Lowell, Lowell, MA, 01854, USA
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3
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Jin H, Wang H, Feng X, Ma X, Zhai Z, Hao Y. Bifidobacterium longum BL300 alleviates DSS-induced Colitis by promoting IgA-mediated Gut Microbiota homeostasis. Food Funct 2025. [PMID: 40350789 DOI: 10.1039/d5fo00992h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Inflammatory bowel disease (IBD) is a chronic disease that is related to excessive inflammation and an imbalance in the gut microbiota. In this study, the effect of five Bifidobacterium longum subsp. longum strains on alleviating the colitis induced by dextran sulfate sodium (DSS) was investigated. Disease activity index (DAI) scores combined with hematoxylin and eosin (H&E) analysis showed that only B. longum BL300 could significantly alleviate DSS-induced colitis. Furthermore, immunofluorescence analysis confirmed that the expression of the intestinal barrier-related protein ZO-1, occludin, claudin-1 and MUC2 was significantly up-regulated. Moreover, transcriptome analysis of the colon tissue combined with RT-qPCR analysis revealed that levels of pro-inflammatory cytokines IL-2, IL-6, IL-17, TNF-α and IL-1β were decreased and anti-inflammatory cytokine IL-10 level was increased after B. longum BL300 intervention. Notably, the IgA production immune network was activated by B. longum BL300, which eliminated pathogenic bacteria, such as Escherichia, Shigella, Enterobacter and Prosthecobacter, by forming complexes. Meanwhile, the relative abundance of SCFA-producing bacteria was significantly increased. These results highlight the anti-inflammatory effect of B. longum BL300 on DSS-induced colitis, indicating its use as a probiotic candidate to support recovery from ongoing colitis.
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Affiliation(s)
- Haowen Jin
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
| | - Hui Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xin Feng
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xin Ma
- Thankcome Research Center for Human Microbiota and Nutritional Health, Suzhou 511450, China
| | - Zhengyuan Zhai
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yanling Hao
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
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4
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Wang G, Wang Y, Sheng K, Wang Y. Effect of probiotic extracellular vesicles and their applications on health and disease. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:3539-3549. [PMID: 39806860 DOI: 10.1002/jsfa.14123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 07/25/2024] [Accepted: 12/31/2024] [Indexed: 01/16/2025]
Abstract
Probiotics have been established to exert a positive impact on the treatment of various diseases. Indeed, these active microorganisms have garnered significant attention in recent years for their potential to prevent and treat illnesses. Their beneficial effects have been hypothesized to be linked to their released extracellular vesicles. These nanoscale structures, secreted during the growth and metabolism of probiotics, possess favorable biocompatibility and targeting properties, thereby promoting intercellular material transport and signaling. This article aimed to review the bioactive components and functions of these probiotics vesicles, highlighting their role in the treatment of various diseases and discussing their potential future applications. By exploring the mechanisms of probiotic extracellular vesicles in disease development, this review aimed to provide a theoretical reference for further research on their therapeutic potential. © 2025 Society of Chemical Industry.
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Affiliation(s)
- Guangzhao Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Yang Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Kangliang Sheng
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Yongzhong Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
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5
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Ofori‐Kwafo A, Sigdel I, Al Mamun E, Zubcevic J, Tang Y. Gut-on-a-chip platforms: Bridging in vitro and in vivo models for advanced gastrointestinal research. Physiol Rep 2025; 13:e70356. [PMID: 40323242 PMCID: PMC12051376 DOI: 10.14814/phy2.70356] [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: 01/23/2025] [Revised: 04/11/2025] [Accepted: 04/22/2025] [Indexed: 05/08/2025] Open
Abstract
The gastrointestinal (GI) tract plays a critical role in nutrient absorption, immune responses, and overall health. Traditional models such as two-dimensional cell cultures have provided valuable insights but fail to replicate the dynamic and complex microenvironment of the human gut. Gut-on-a-chip platforms, which incorporate cells located in the gut into microfluidic devices that simulate peristaltic motion and fluid flow, represent a significant advancement in modeling GI physiology and diseases. This review discusses the evolution of gut-on-a-chip technology, from simple cellular mono-cultures models to more sophisticated systems incorporating bi-cultures and tri-cultures that enable studies of drug metabolism, disease modeling, and gut-microbiome interactions. Although challenges remain, including maintaining long-term cell viability and replicating immune responses, these platforms hold great potential for advancing personalized medicine and improving drug discovery efforts targeting gastrointestinal disorders.
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Affiliation(s)
- Awurama Ofori‐Kwafo
- Department of Bioengineering, College of EngineeringUniversity of ToledoToledoOhioUSA
| | - Indira Sigdel
- Department of Bioengineering, College of EngineeringUniversity of ToledoToledoOhioUSA
| | - Earshed Al Mamun
- Department of Bioengineering, College of EngineeringUniversity of ToledoToledoOhioUSA
| | - Jasenka Zubcevic
- University of South Florida Center for Microbiome ResearchMicrobiomes InstituteTampaFloridaUSA
- Department of Neurosurgery and Brain RepairUniversity of South Florida Morsani College of MedicineTampaFloridaUSA
| | - Yuan Tang
- Department of Bioengineering, College of EngineeringUniversity of ToledoToledoOhioUSA
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6
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Yu S, Zhu X, Zhao X, Li Y, Niu X, Chen Y, Ying J. Improvement of chronic metabolic inflammation and regulation of gut homeostasis: Tea as a potential therapy. Pharmacol Ther 2025; 269:108828. [PMID: 40020787 DOI: 10.1016/j.pharmthera.2025.108828] [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: 04/30/2024] [Revised: 12/27/2024] [Accepted: 02/21/2025] [Indexed: 03/03/2025]
Abstract
Chronic metabolic inflammation is a common mechanism linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease (CVD). Chronic metabolic inflammation often related to alterations in gut homeostasis, and pathological processes involve the activation of endotoxin receptors, metabolic reprogramming, mitochondrial dysfunction, and disruption of intestinal nuclear receptor activity. Recent investigations into homeostasis and chronic metabolic inflammation have revealed a novel mechanism which is characterized by a timing interaction involving multiple components and targets. This article explores the positive impact of tea consumption on metabolic health of populations, with a special focus on the improvement of inflammatory indicators and the regulation of gut microbiota. Studies showed that tea consumption is related to the enrichment of gut microbiota. The relative proportion of Firmicutes/Bacteroidetes (F/B) is altered, while the abundance of Lactobacillus, Bifidobacterium, and A. muciniphila increased significantly in most of the studies. Thus, tea consumption could provide potential protection from the development of chronic diseases by improving gut homeostasis and reducing chronic metabolic inflammation. The direct impact of tea on intestinal homeostasis primarily targets lipopolysaccharide (LPS)-related pathways. This includes reducing the synthesis of intestinal LPS, inhibiting LPS translocation, and preventing the binding of LPS to TLR4 receptors to block downstream inflammatory pathways. The TLR4/MyD88/NF-κB p65 pathway is crucial for anti-metaflammatory responses. The antioxidant properties of tea are linked to enhancing mitochondrial function and mitigating mitochondria-related inflammation by eliminating free radicals, inhibiting NLRP3 inflammasomes, and modulating Nrf2/ARE activity. Tea also contributes to safeguarding the intestinal barrier through various mechanisms, such as promoting the synthesis of short-chain fatty acids in the intestine, activating intestinal aryl hydrocarbon receptor (AhR) and farnesoid X receptor (FXR), and improving enteritis. Functional components that improve chronic metabolic inflammation include tea polyphenols, tea pigments, TPS, etc. Tea metabolites such as 4-Hydroxyphenylacetic acid and 3,4-Dihydroxyflavan derivatives, etc., also contribute to anti-chronic metabolic inflammation effects of tea consumption. The raw materials and processing technologies affect the functional component compositions of tea; therefore, consuming different types of tea may result in varying action characteristics and mechanisms. However, there is currently limited elaboration on this aspect. Future research should conduct in-depth studies on the mechanism of tea and its functional components in improving chronic metabolic inflammation. Researchers should pay attention to whether there are interactions between tea and other foods or drugs, explore safe and effective usage and dosage, and investigate whether there are individual differences in the tea-drinking population leading to different effects of tea intervention. Ultimately, the application of tea drinking could be a universal therapy for regulating intestinal homeostasis, anti-chronic metabolic inflammatory responses, and promoting metabolic health.
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Affiliation(s)
- Shiyi Yu
- Nutrition and Health Research Institute, School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430000, China
| | - Xuan Zhu
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China
| | - Xiayu Zhao
- National Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Yan Li
- National Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xinghe Niu
- Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China; COFCO Nutrition and Health Research Institute, Beijing 102209, China
| | - Yinghua Chen
- Nutrition and Health Research Institute, School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430000, China
| | - Jian Ying
- Nutrition and Health Research Institute, School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430000, China.
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7
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Hua S, Zhang Z, Zhang Z, Liu L, Yu S, Xiao Y, Liu Y, Wei S, Xu Y, Chen YG. Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation. EMBO Rep 2025:10.1038/s44319-025-00464-y. [PMID: 40307620 DOI: 10.1038/s44319-025-00464-y] [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: 09/07/2024] [Revised: 04/12/2025] [Accepted: 04/16/2025] [Indexed: 05/02/2025] Open
Abstract
Disruption of the circadian clock is associated with the development of inflammatory bowel disease (IBD), but the underlying mechanisms remain unclear. Here, we observe that mice in the early active phase (Zeitgeber time 12, ZT12) of the circadian clock are more tolerant to dextran sodium sulfate (DSS)-induced colitis, compared to those in the early resting phase (ZT0). The expression of the circadian gene Bmal1 peaks in the early resting phase and declines in the early active phase. Bmal1 knockout in the intestinal epithelium reduces DSS-induced inflammatory symptoms. Mechanistically, BMAL1 promotes apoptosis by binding to apoptosis-related genes, including Bax, p53, and Bak1, and promotes their expression. Intriguingly, we observe circadian apoptotic rhythms in the homeostatic intestinal epithelium, while Bmal1 deletion reduces cell apoptosis. Consistently, reducing Bmal1 expression by the REV-ERBα agonist SR9009 has the best therapeutic efficacy against DSS-induced colitis at ZT0. Collectively, our data demonstrate that the Bmal1-centered circadian clock is involved in intestinal injury repair.
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Affiliation(s)
- Shan Hua
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Ze Zhang
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Zhe Zhang
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Liansheng Liu
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Shicheng Yu
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Yanhui Xiao
- Guangzhou National Laboratory, Guangzhou, 510005, China
| | - Yuan Liu
- The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Siting Wei
- The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Ying Xu
- Cambridge-Su Genomic Resource Center, Soochow University, Suzhou, Jiangsu, 215123, China
| | - Ye-Guang Chen
- Guangzhou National Laboratory, Guangzhou, 510005, China.
- The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China.
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8
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Lin W, Ruishi X, Caijiao X, Haoming L, Xuefeng H, Jiyou Y, Minqiang L, Shuo Z, Ming Z, Dongyang L, Xiaoxue F. Potential applications and mechanisms of natural products in mucosal-related diseases. Front Immunol 2025; 16:1594224. [PMID: 40370438 PMCID: PMC12075308 DOI: 10.3389/fimmu.2025.1594224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Accepted: 04/09/2025] [Indexed: 05/16/2025] Open
Abstract
The mucosal barrier serves as a crucial defense against external pathogens and allergens, being widely distributed across the respiratory, gastrointestinal, urogenital tracts, and oral cavity. Its disruption can lead to various diseases, including inflammatory bowel disease, asthma, urinary tract infections, and oral inflammation. Current mainstream treatments for mucosa-associated diseases primarily involve glucocorticoids and immunosuppressants, but their long-term use may cause adverse effects. Therefore, the development of safer and more effective therapeutic strategies has become a focus of research. Natural products, with their multi-target and multi-system regulatory advantages, offer a promising avenue for the treatment of mucosal diseases. This review summarizes the potential applications of natural products in diseases of mucosal barrier dysfunction through mechanisms such as immune modulation, inflammation inhibition, tight junction protein restoration, and gut microbiota regulation, with the aim of providing insights for the exploration of novel therapeutic strategies.
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Affiliation(s)
- Wang Lin
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xie Ruishi
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xu Caijiao
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Luo Haoming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Hua Xuefeng
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Yao Jiyou
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Lu Minqiang
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Zhou Shuo
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Zhu Ming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Li Dongyang
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Fang Xiaoxue
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
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9
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Luo D, Luo G, Xu H, Li K, Li Z, Zhang C. Inorganic dietary nanoparticles in intestinal barrier function of inflammatory bowel disease: allies or adversaries? Front Immunol 2025; 16:1563504. [PMID: 40270957 PMCID: PMC12014688 DOI: 10.3389/fimmu.2025.1563504] [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: 01/20/2025] [Accepted: 03/24/2025] [Indexed: 04/25/2025] Open
Abstract
Inorganic dietary nanoparticles (IDNPs) are frequently utilized as food additives and in packaging, resulting in their exposure becoming a substantial yet often overlooked concern for patients with inflammatory bowel disease (IBD). Considering that impaired intestinal barrier function plays a central role in the pathogenesis of IBD, this review concentrates on the roles and mechanisms of IDNPs in the intestinal barrier (physical, chemical, biological, and immune barriers) of IBD patients. Previous studies have shown that different types of nanoparticles have varying effects on animals in diverse states. In this context, factors such as the source, size, shape, dosage, and duration of action of the nanoparticles, as well as the species, gender, dietary habits, and age of the animals, significantly influence research outcomes. Future studies should undertake more comprehensive explorations into the effects and mechanisms of IDNPs with diverse sources and properties in IBD patients.
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Affiliation(s)
- Duo Luo
- Department of Geriatrics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
| | - Guifang Luo
- Department of Geriatrics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
| | - Haoming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
| | - Kangbao Li
- Department of Geriatrics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
| | - Zhaotao Li
- Department of Gastroenterology, The First People’s Hospital of Foshan, Foshan, China
| | - Cong Zhang
- Department of Gastroenterology, The First People’s Hospital of Foshan, Foshan, China
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10
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Muro P, Jing C, Zhao Z, Jin T, Mao F. The emerging role of honeysuckle flower in inflammatory bowel disease. Front Nutr 2025; 12:1525675. [PMID: 40225345 PMCID: PMC11985448 DOI: 10.3389/fnut.2025.1525675] [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: 11/10/2024] [Accepted: 03/13/2025] [Indexed: 04/15/2025] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC), referred to as inflammatory bowel disease (IBD), pose considerable challenges in treatment because they are chronic conditions that easily relapse. The occurrence of IBD continues to rise in developing countries. Nonetheless, the existing therapies for IBD have limitations and fail to address the needs of the patients thoroughly. There is an increasing need for new, safe, and highly effective alternative medications for IBD patients. Traditional Chinese Medicine (TCM) is employed in drug development and disease management due to its wide-range of biological activities, minimal toxicity, and limited side effects. Extensive research has shown that certain TCM exhibits significant therapeutic benefits for IBD treatments. Honeysuckle (Lonicera japonica) was used in TCM research and clinical settings for the treatment of IBD. Bioactive metabolites in L. japonica, such as luteolin, quercetin, cyanidin, chlorogenic acid (CGA), caffeic acid (CA), and saponin, exhibit significant therapeutic benefits for managing IBD. The honeysuckle flower is a potential candidate in the treatment of IBD due to its anti-inflammatory, immune system-regulating, and antioxidant qualities. This paper reviews the metabolites of the honeysuckle flower as a candidate for the treatment of IBD. It discusses the fundamental mechanism of L. japonica and the potential of its bioactive metabolites in the prevention and treatment of IBD.
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Affiliation(s)
- Peter Muro
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Caihong Jing
- The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, Jiangsu, China
| | - Zhihan Zhao
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Tao Jin
- Department of Gastrointestinal and Endoscopy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Fei Mao
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
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11
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Jiang X, Ren J, Yu G, Wu W, Chen M, Zhao Y, He C. Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis. Nutrients 2025; 17:1174. [PMID: 40218932 PMCID: PMC11990178 DOI: 10.3390/nu17071174] [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: 02/24/2025] [Revised: 03/19/2025] [Accepted: 03/26/2025] [Indexed: 04/14/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colorectum, posing a significant global health burden. Recent studies highlight the critical role of gut microbiota and its metabolites, particularly bile acids (BAs), in UC's pathogenesis. The relationship between BAs and gut microbiota is bidirectional: microbiota influence BA composition, while BAs regulate microbiota diversity and activity through receptors like Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Targeting bile-acid metabolism to reshape gut microbiota presents a promising therapeutic strategy for UC. This review examines the classification and synthesis of BAs, their interactions with gut microbiota, and the potential of nutritional and microbial interventions. By focusing on these therapies, we aim to offer innovative approaches for effective UC management.
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Affiliation(s)
| | | | | | | | | | | | - Canxia He
- School of Public Health, Health Science Center, Ningbo University, Ningbo 315211, China
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12
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Cao R, Zhou J, Liu J, Wang Y, Dai Y, Jiang Y, Yamauchi A, Atlas D, Jin T, Zhou J, Wang C, Tan Q, Chen Y, Yodoi J, Tian H. TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways. Inflammation 2025:10.1007/s10753-025-02282-9. [PMID: 40085192 DOI: 10.1007/s10753-025-02282-9] [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: 05/31/2024] [Revised: 02/11/2025] [Accepted: 03/02/2025] [Indexed: 03/16/2025]
Abstract
The activation of inflammasomes (NLRP3 and NLRP1) is central to the pathogenesis of inflammatory bowel disease (IBD). Here we examined the protective effects of a thioredoxin-mimetic peptide CB13 (TXM-CB13), known for its antioxidative stress and anti-inflammatory properties. We examined the effects of TXM-CB13 on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation in RAW264.7 macrophages. TXM-CB13 appeared to alleviate symptoms of DSS-induced colitis and to significantly suppress the protein and mRNA levels of NLRP3, Mlck, and IL-1β in colonic tissues. Additionally, TXM-CB13 treatment increased the levels of the intestinal barrier proteins Occludin, ZO-1, and NLRP1, as shown through immunohistochemistry and Western blot analysis. In vitro, TXM-CB13 inhibited LPS-induced TLR4 signaling, reducing MyD88 levels and consequently attenuating the activation of the NF-κB pathways, including p-IκB-α/IκB-α and p-NF-κB-p65/NF-κB-p65. This inhibition further reduced the activation of the NLRP3 inflammasome components, NLRP3, ASC, Caspase-1, GSDMD, and IL-1β. In addition, TXM-CB13 prevented the ROS-mediated dissociation of TXNIP from TRX, inhibiting NLRP3 activation. These findings suggest that TXM-CB13 is a potential therapeutic candidate for IBD through its modulation of the TLR4/MyD88/NF-κB/NLRP3 and ROS/TXNIP/TRX/NLRP3 pathways.
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Affiliation(s)
- Ruijie Cao
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Jinhui Zhou
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Jiale Liu
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Yaxuan Wang
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Yandong Dai
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Yun Jiang
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Akira Yamauchi
- Department of Breast Surgery, Misugi-kai Sato Hospital Breast Center, HIrakata, Osaka, Japan
| | - Daphne Atlas
- Dept. Of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel
| | - Tiancheng Jin
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Jiedong Zhou
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Cuixue Wang
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Qihuan Tan
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Yifei Chen
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China
| | - Junji Yodoi
- Laboratory of Infection and Prevention, Department of Biological Response, Institute for Virus Research, Kyoto University, Kyoto, Japan
| | - Hai Tian
- Department of Basic Medicine, Medical College, Shaoxing University, Shaoxing, China.
- Jiaozhimei Biotechnology (Shaoxing) Co., Ltd., Shaoxing, China.
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13
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Liu MC, Shu YA, Wang YC, Tseng HY, Li MJ, Yu YT, Cheng HC, Tsai PJ, Yang YJ. Faecalibacterium prausnitzii Colonization Attenuates Gut Inflammation and Epithelial Damage in a DSS-Induced Colitis Mice Model. Mediators Inflamm 2025; 2025:7280675. [PMID: 40224484 PMCID: PMC11986197 DOI: 10.1155/mi/7280675] [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: 09/30/2024] [Accepted: 02/04/2025] [Indexed: 04/15/2025] Open
Abstract
Background: Reduction of Faecalibacterium prausnitzii abundance is related to inflammatory bowel diseases (IBDs), and supplement of it exists protective effects. Aim: This study aimed to establish a F. prausnitzii-colonized mouse model and investigate that the presence of F. prausnitzii in the gut can ameliorate the severity of dextran sulfate sodium (DSS)-induced colitis. Methods: A F. prausnitzii (ATCC 27768) strain was maintained on the PS-BHI agar plates and manipulated in a strictly anaerobic chamber. A F. prausnitzii-colonized C57BL/6 mice model was tested by a rectal enema with 1 × 109 bacteria/day for 3 days. The 5% DSS was added to drinking water for 3 days to induce colitis and diarrhea in experimental mice. The clinical, cytological, and histological severities were compared between groups. Results: The F. prausnitzii-colonized mice model was successfully established via rectal enema with the property of transfer to offspring. DSS treatment altered gut microbiota and significantly attenuated the abundance of F. prausnitzii in colonized mice. Mice with F. prausnitzii colonization had significantly improved weight loss, anal bleeding, stool consistency, cecum weight, colon length, and serum amyloid A (SAA) level than those without after DSS treatment. Furthermore, the F. prausnitzii-colonized mice significantly reduced the transcription levels of TNF-α, INF-γ and IL-18, and epithelial damage and PMN infiltration in the lamina propria and had better preservation of goblet cells than the control group. Conclusion: We have successfully established a mouse model colonized with F. prausnitzii via rectal enema administration and showed colonization of F. prausnitzii in the gut has a protective effect against DSS-induced colitis.
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Affiliation(s)
- Meng-Chuan Liu
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-An Shu
- Department of Medical Laboratory Science and Biotechnology and Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Chin Wang
- Department of Medical Laboratory Science and Biotechnology and Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Hsiu-Ying Tseng
- Department of Medical Laboratory Science and Biotechnology and Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Jia Li
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Ting Yu
- Department of Pathology, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsiu-Chi Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology and Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yao-Jong Yang
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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14
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Donetti E, Bendinelli P, Correnti M, Gammella E, Recalcati S, Ferraretto A. Caco2/HT-29 In Vitro Cell Co-Culture: Barrier Integrity, Permeability, and Tight Junctions' Composition During Progressive Passages of Parental Cells. BIOLOGY 2025; 14:267. [PMID: 40136523 PMCID: PMC11939685 DOI: 10.3390/biology14030267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 02/28/2025] [Accepted: 03/02/2025] [Indexed: 03/27/2025]
Abstract
Epithelial linings are crucial for the maintenance of physiological barriers. The intestinal epithelial barrier (IEB) consists of enterocytes through tight junctions and mucus-secreting cells and can undergo physiological modifications throughout life. To reproduce as closely as possible the IEB main features over time, in vitro co-cultures of Caco2/HT-29 70/30 formed by parental Caco2 and HT-29 cells sub-cultivated for more than 40 passages were set up. The measurements of the transepithelial electrical resistance (TEER) identified two populations: physiological TEER co-cultures (PC) with values > 50 Ωcm2 formed by parental cells with fewer than 40 passages, and leaky TEER co-cultures (LC) with values < 50 Ωcm2 formed by parental cells with more than 40 passages. In LC, paracellular permeability increased in parallel. By immunofluorescence and Western blot analysis, an increase in claudin 2 was observed in LC vs. PC, with no differences in occludin expression. MUC-2 immunoreactivity was stronger in PC than in LC. LC also showed an enhanced vulnerability to TNFα+IFN-γ. These results reproduce the main morpho-functional modifications reported in the human leaky/aged gut and support the usefulness of our in vitro cell model for studying the molecular processes underlying these modifications and testing drug/nutraceutical treatments to ameliorate leaky gut aging.
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15
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Wang W, Chen Y, Wang Y, Wang Y, Zhang W, Dai K, Geng W, Tang S. Azo-linked 5-ASA-coumarin prodrug: Fluorescent tracking for colonic drug release in UC treatment. Talanta 2025; 284:127277. [PMID: 39608145 DOI: 10.1016/j.talanta.2024.127277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/12/2024] [Accepted: 11/21/2024] [Indexed: 11/30/2024]
Abstract
Theranostic prodrugs that enable real-time, non-invasive monitoring of drug release and biodistribution are highly desirable for optimizing therapeutic efficacy and guiding personalized medication. Herein, we report a colon-targeted theranostic prodrug system (P1) for the simultaneous delivery and tracking of 5-aminosalicylic acid (5-ASA) in the treatment of ulcerative colitis (UC). P1 comprises a fluorescent 7-amino-4-methylcoumarin (7-AMC) reporter covalently linked to 5-ASA via an azo bond, which quenches the fluorescence of 7-AMC until P1 is activated by azoreductases in the colonic microenvironment. This selective activation triggers the release of 5-ASA and the revival of 7-AMC fluorescence, enabling real-time monitoring of drug delivery. To improve the solubility and targeted delivery of P1, it was encapsulated within polymeric micelles (PM) that selectively adhere to the positively charged, inflamed colonic tissues. In vitro studies confirmed the stability, biocompatibility, and selective activation of P1 under simulated colonic conditions. Notably, in a mouse model of UC, the P1-loaded PM achieved targeted delivery of 5-ASA to the inflamed colon, resulting in effective attenuation of colitis symptoms. Importantly, the in situ activation of P1 allowed for the real-time, non-invasive visualization of drug release and biodistribution, providing valuable insights for treatment optimization. This theranostic prodrug approach offers a promising strategy for the simultaneous therapy and tracking of 5-ASA delivery in UC treatment, with the potential to facilitate personalized medication and improve therapeutic outcomes.
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Affiliation(s)
- Wenchao Wang
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and BrainHealth), Wenzhou Medical University, Zhejiang, China
| | - Yingjie Chen
- Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China; University of Chinese Academy of Sciences, Wenzhou Institute, Zhejiang, China
| | - Yuan Wang
- University of Chinese Academy of Sciences, Wenzhou Institute, Zhejiang, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, China
| | - Yijian Wang
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and BrainHealth), Wenzhou Medical University, Zhejiang, China
| | - Wenjing Zhang
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and BrainHealth), Wenzhou Medical University, Zhejiang, China
| | - Keke Dai
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and BrainHealth), Wenzhou Medical University, Zhejiang, China
| | - Wujun Geng
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and BrainHealth), Wenzhou Medical University, Zhejiang, China.
| | - Sicheng Tang
- University of Chinese Academy of Sciences, Wenzhou Institute, Zhejiang, China.
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16
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Lundquist P, Hagforsen E, Wagner M, Alimohammadi M, Melo FR, Pejler G, Artursson P, Carlson M, Rollman O, Lampinen M. Mild-to-moderate psoriasis is associated with subclinical inflammation in the duodenum and a tendency of disturbed intestinal barrier. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167634. [PMID: 39706352 DOI: 10.1016/j.bbadis.2024.167634] [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: 05/27/2024] [Revised: 11/01/2024] [Accepted: 12/15/2024] [Indexed: 12/23/2024]
Abstract
Psoriasis is a chronic skin disease occasionally associated with abdominal symptoms and IBD. We aimed to characterize intestinal immune cells and the integrity of the intestinal barrier in psoriasis. Biopsies from the duodenum and colon were analyzed by flow cytometry and immunohistochemistry for the presence and activation status of different immune cell populations. Intestinal permeability was measured using Ussing chambers. Proinflammatory markers were analyzed in fecal and blood samples using ELISA. The intestinal level of inflammatory mediators was assessed using a multiplex proximity extension assay. We found an increased density of intestinal eosinophils, mast cells, macrophages, and CD8+ T-cells in psoriasis; eosinophils, macrophages, and CD8+ T-cells expressed activation markers. Half of the psoriasis patients showed increased permeability across the duodenum, correlating with increased mucosal IL-17A, IL-13, IL-2, and IL-20, and with gastrointestinal symptoms. Our findings reveal that psoriasis is associated with low-grade intestinal inflammation, which may contribute to abdominal symptoms in these patients and possibly set the stage for the development of intestinal disease.
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Affiliation(s)
- Patrik Lundquist
- Department of Pharmacy, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden
| | - Eva Hagforsen
- Dermatology and Venereology, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Michael Wagner
- Gastroenterology Research Group, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Mohammad Alimohammadi
- Dermatology and Venereology, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Fabio Rabelo Melo
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden
| | - Gunnar Pejler
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden
| | - Per Artursson
- Department of Pharmacy, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden
| | - Marie Carlson
- Gastroenterology Research Group, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Ola Rollman
- Dermatology and Venereology, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
| | - Maria Lampinen
- Department of Pharmacy, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden; Gastroenterology Research Group, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
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17
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Li W, He X, Tan C, Zhang T. Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study. Am J Med Genet B Neuropsychiatr Genet 2025; 198:e33012. [PMID: 39350682 DOI: 10.1002/ajmg.b.33012] [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: 02/28/2024] [Revised: 07/15/2024] [Accepted: 09/20/2024] [Indexed: 02/11/2025]
Abstract
Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.
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Affiliation(s)
- Weilin Li
- Department of Anorectal Surgery, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xiaoyu He
- Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chao Tan
- Department of Internal Medicine, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Tao Zhang
- Graduate School, Hunan University of Chinese Medicine, Changsha, China
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18
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Kerezoudi EN, Zervakis GI, Pletsa V, Kyriacou A, Brummer RJ, Rangel I. Pleurotus eryngii Mushrooms Fermented with Human Fecal Microbiota Protect Intestinal Barrier Integrity: Immune Modulation and Signalling Pathways Counter Deoxycholic Acid-Induced Disruption in Healthy Colonic Tissue. Nutrients 2025; 17:694. [PMID: 40005021 PMCID: PMC11858169 DOI: 10.3390/nu17040694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Background: This study explores the potential of the Pleurotus eryngii mushroom fermentation supernatant (FS-PEWS) as an intervention for mitigating sodium deoxycholate (SDC)-induced intestinal barrier dysfunction and inflammation. Methods: FS-PEWS was assessed for its protective effects against SDC-induced barrier dysfunction and inflammation using an in vitro Caco-2 cell model and ex vivo colonic biopsies from healthy adult donors, where barrier integrity, permeability, immunomodulation and receptor-mediated pathways were evaluated. Results: In Caco-2 cells, SDC exposure downregulated ZO-1, occludin, and claudin-1 expression, with FS-PEWS restoring ZO-1 and claudin-1 levels while maintaining cell viability. In colonic biopsies from healthy adults, FS-PEWS maintained tissue integrity and selectively mitigated transcellular permeability without affecting paracellular permeability when combined with the stressor. Additionally, FS-PEWS exhibited potent anti-inflammatory effects, reducing pro-inflammatory cytokines, e.g., TNF-α, IL-6, and IL-1β and modulating receptor-mediated pathways, i.e., TLR-4, dectin-1. Conclusions: These results demonstrate the potential of FS-PEWS to sustain intestinal barrier function and modulate immune responses under stress, highlighting its therapeutic potential for managing gut barrier dysfunction and inflammation associated with microbial metabolite-induced disruptions.
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Affiliation(s)
- Evangelia N. Kerezoudi
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
- Department of Nutrition and Dietetics, Harokopio University, 17676 Athens, Greece;
| | - Georgios I. Zervakis
- Laboratory of General and Agricultural Microbiology, Department of Crop Science, Agricultural University of Athens, 11855 Athens, Greece;
| | - Vasiliki Pletsa
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece;
| | - Adamantini Kyriacou
- Department of Nutrition and Dietetics, Harokopio University, 17676 Athens, Greece;
| | - Robert J. Brummer
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
| | - Ignacio Rangel
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
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19
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Ülfer G, Polat B, Yabalak A, Çakıcı Ç. Evaluation of zonulin levels in patients with migraine. BMC Neurol 2025; 25:46. [PMID: 39905280 PMCID: PMC11792365 DOI: 10.1186/s12883-025-04058-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/28/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Zonulin regulates permeability in blood-brain and intestinal barriers. The pathophysiology of migraine is based on the effect of neurogenic inflammation. The aim of the current investigation was to examine the serum zonulin level in individuals suffering from migraine. METHODS The sample comprised 40 individuals who had migraine and 40 controls. Disease duration, attack duration, attack frequency, Visual Analog Scale (VAS) scores, and comorbidities were available for the migraine group. Serum zonulin levels were evaluated by using the ELISA method. RESULTS There were no statistically significant differences between the two groups concerning age or gender (p > 0.05). The zonulin value of patients with migraine was higher when compared to the controls, indicating a significant difference (p = 0.037; p < 0.05). The zonulin level did not correlate with disease duration, attack duration, VAS score, or attack frequency (p > 0.05). The receiver operating characteristic curve analysis of zonulin revealed a cut-off value of 30.58 and above, at which it had 52.50% sensitivity, 77.5% specificity, 70% positive predictive value, and 62% a negative predictive value. The area under the curve was 63.6%, and the standard error value was 6.3%. The analysis also showed a statistically significant correlation between migraine diagnosis and a zonulin level of 30.58 (p = 0.006; p < 0.01). CONCLUSIONS Elevated zonulin levels in patients with migraine support the disruption of the intestinal barrier and neuroinflammation in these patients. The zonulin level may be a predictive biomarker of migraine. Multicenter, randomized trials are needed to evaluate treatments for intestinal permeability and zonulin levels in migraine patients.
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Affiliation(s)
- Gözde Ülfer
- Faculty of Medicine, Department of Biochemistry, İstanbul Medipol University, İstanbul, Turkey.
| | - Burcu Polat
- Department of Neurology, Duzce University Faculty of Medicine, Düzce, Turkey
| | - Ahmet Yabalak
- Department of Neurology, Duzce University Faculty of Medicine, Düzce, Turkey
| | - Çağrı Çakıcı
- Faculty of Medicine, Department of Biochemistry, İstanbul Medipol University, İstanbul, Turkey
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20
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Escalante J, Artaiz O, Diwakarla S, McQuade RM. Leaky gut in systemic inflammation: exploring the link between gastrointestinal disorders and age-related diseases. GeroScience 2025; 47:1-22. [PMID: 39638978 PMCID: PMC11872833 DOI: 10.1007/s11357-024-01451-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/20/2024] [Indexed: 12/07/2024] Open
Abstract
Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated with aging. Osteoarthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and cognitive decline associated with dementia are among the most common age-related diseases and contribute significantly to morbidity and mortality in the aged population. Many of these age-related diseases have been linked to chronic low-grade systemic inflammation which often accompanies aging. Gastrointestinal barrier dysfunction, also known as "leaky gut," has been shown to contribute to systemic inflammation in several diseases including inflammatory bowel disease and irritable bowel syndrome, but its role in the development and/or progression of chronic low-grade systemic inflammation during aging is unclear. This review outlines current literature on the leaky gut in aging, how leaky gut might contribute to systemic inflammation, and the links between gastrointestinal inflammatory diseases and common age-related diseases to provide insight into a potential relationship between the intestinal barrier and inflammation.
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Affiliation(s)
- Jonathan Escalante
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
| | - Olivia Artaiz
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
| | - Shanti Diwakarla
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
- The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia
| | - Rachel M McQuade
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia.
- The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia.
- Australian Institute for Musculoskeletal Science (AIMSS), The Melbourne University and Western Health, Melbourne, VIC, 3021, Australia.
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21
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Nakamura A, Matsumoto M. Role of polyamines in intestinal mucosal barrier function. Semin Immunopathol 2025; 47:9. [PMID: 39836273 PMCID: PMC11750915 DOI: 10.1007/s00281-024-01035-4] [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: 04/08/2024] [Accepted: 12/27/2024] [Indexed: 01/22/2025]
Abstract
The intestinal epithelium is a rapidly self-renewing tissue; the rapid turnover prevents the invasion of pathogens and harmful components from the intestinal lumen, preventing inflammation and infectious diseases. Intestinal epithelial barrier function depends on the epithelial cell proliferation and junctions, as well as the state of the immune system in the lamina propria. Polyamines, particularly putrescine, spermidine, and spermine, are essential for many cell functions and play a crucial role in mammalian cellular homeostasis, such as that of cell growth, proliferation, differentiation, and maintenance, through multiple biological processes, including translation, transcription, and autophagy. Although the vital role of polyamines in normal intestinal epithelial cell growth and barrier function has been known since the 1980s, recent studies have provided new insights into this topic at the molecular level, such as eukaryotic initiation factor-5A hypusination and autophagy, with rapid advances in polyamine biology in normal cells using biological technologies. This review summarizes recent advances in our understanding of the role of polyamines in regulating normal, non-cancerous, intestinal epithelial barrier function, with a particular focus on intestinal epithelial renewal, cell junctions, and immune cell differentiation in the lamina propria.
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Affiliation(s)
- Atsuo Nakamura
- Dairy Science and Technology Institute, Kyodo Milk Industry Co. Ltd, 20-1 Hirai, Hinode-Machi, Nishitama-Gun, Tokyo, 190-0182, Japan
| | - Mitsuharu Matsumoto
- Dairy Science and Technology Institute, Kyodo Milk Industry Co. Ltd, 20-1 Hirai, Hinode-Machi, Nishitama-Gun, Tokyo, 190-0182, Japan.
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Cai R, Zheng Y, Lane JA, Huang P, Hu R, Huang Q, Liu F, Zhang B. In Vitro Infant Fecal Fermentation Metabolites of Osteopontin and 2'-Fucosyllactose Support Intestinal Barrier Function. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:1642-1655. [PMID: 39705716 DOI: 10.1021/acs.jafc.4c07683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2024]
Abstract
In this study, we investigated the effects of infant fecal fermentation-derived metabolites of digested osteopontin (OPN) and 2'-fucosyllactose (2'-FL), either individually or in combination, on intestinal barrier function using a Caco-2/HT-29 coculture cell model. Our results suggested that the OPN/2'-FL (1:36-1:3) cofermentation metabolites improved epithelial barrier integrity by supporting the mRNA and protein expression of occludin, claudin-1, claudin-2, ZO-1, and ZO-2. All of the OPN/2'-FL treatments decreased the production of IL-1β, IL-6, and TNF-α, while the OPN/2'-FL ratio increased IL-10 production by inhibiting activation of the MyD88/IκB-α/NF-κB signaling pathway. OPN/2'-FL cofermentation altered the metabolic pathways, and the protective effect of fermentation metabolites on intestinal barrier function was related to differential metabolite expression such as short-chain fatty acids, deoxycholic acid, and 4-aminobutyric acid. Our findings provide in vitro evidence to support the application of the OPN/2'-FL combination in infant formula for the advancement of formulation functionality, including intestinal barrier function.
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Affiliation(s)
- Ran Cai
- School of Food Science and Engineering, Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health, South China University of Technology, Guangzhou 510640, China
- Sino-Singapore International Research Institute, Guangzhou 510555, China
| | - Yuxing Zheng
- H&H Research, China Research and Innovation Center, H&H Group, Guangzhou 510700, China
| | - Jonathan A Lane
- H&H Research, Global Research and Technology Centre, H&H Group, P61 K202 Co. Cork, Ireland
| | - Pantian Huang
- H&H Research, China Research and Innovation Center, H&H Group, Guangzhou 510700, China
| | - Ruibiao Hu
- H&H Research, China Research and Innovation Center, H&H Group, Guangzhou 510700, China
| | - Qiang Huang
- School of Food Science and Engineering, Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health, South China University of Technology, Guangzhou 510640, China
- Sino-Singapore International Research Institute, Guangzhou 510555, China
| | - Feitong Liu
- H&H Research, China Research and Innovation Center, H&H Group, Guangzhou 510700, China
| | - Bin Zhang
- School of Food Science and Engineering, Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health, South China University of Technology, Guangzhou 510640, China
- Sino-Singapore International Research Institute, Guangzhou 510555, China
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Chen G, Huang T, Dai Y, Huo X, Xu X. Effects of POPs-induced SIRT6 alteration on intestinal mucosal barrier function: A comprehensive review. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 289:117705. [PMID: 39805197 DOI: 10.1016/j.ecoenv.2025.117705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/05/2025] [Accepted: 01/06/2025] [Indexed: 01/16/2025]
Abstract
Persistent organic pollutants (POPs) are pervasive organic chemicals with significant environmental and ecological ramifications, extending to adverse human health effects due to their toxicity and persistence. The intestinal mucosal barrier, a sophisticated defense mechanism comprising the epithelial layer, mucosal chemistry, and cellular immunity, shields the host from external threats and fosters a symbiotic relationship with intestinal bacteria. Sirtuin 6 (SIRT6), a sirtuin family member, is pivotal in genome and telomere stability, inflammation regulation, and metabolic processes. Result shows POPs have been implicated in the intestinal diseases, particularly in intestinal barrier dysfunction, through mechanisms such as cellular damage, epigenetic alterations, inflammation, microbiota changes, and metabolic disruptions. While the impact of SIRT6 expression changes on intestinal barrier functions has been reviewed, the mechanisms linking POPs to SIRT6 remain elusive. This review summarized the latest research results on the effects of POPs on intestinal barrier, discussed the role of SIRT6 from multiple mechanism perspectives, proposed new research directions on POPs, SIRT6 and intestinal health, and explored the therapeutic potential of SIRT6.
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Affiliation(s)
- Guangcan Chen
- Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Digestive Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515000, China
| | - Tengyang Huang
- Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Digestive Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515000, China
| | - Yifeng Dai
- Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands
| | - Xia Huo
- Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangdong, Guangzhou 511443, China
| | - Xijin Xu
- Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China.
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24
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Zeng C, Zhu Q, Peng W, Huang C, Chen H, Huang H, Zhou Y, Zhao C. The protective effect of amitriptyline on experimental colitis through inhibiting TLR-4/MD-2 signaling pathway. J Pharmacol Exp Ther 2025; 392:100024. [PMID: 39892990 DOI: 10.1124/jpet.124.002207] [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: 03/08/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 10/10/2024] Open
Abstract
Amitriptyline, a pleiotropic tricyclic antidepressant, possesses antioxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on inflammatory bowel disease (IBD) are not yet well defined. To explore this, we used a dextran sulfate sodium (DSS)-induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates. Our research revealed that amitriptyline is effective in alleviating several pathological manifestations associated with colitis. This includes improving body weight retention, reducing disease activity index, lessening of colon length shortening, and repairing of colonic mucosal damage. Treatment with amitriptyline significantly protected mucosal injury by preserving the population of goblet cells and increasing the expression of tight junction proteins. Furthermore, we observed that amitriptyline effectively countered immune cell infiltration, specifically neutrophils and macrophages, while simultaneously lowering the levels of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, and IL-6. Additionally, RNA sequencing analysis pointed to the potential involvement of the Toll-like receptor (TLR) pathway in the anticolitic effects induced by amitriptyline. Subsequent Western blot analysis indicated that amitriptyline significantly inhibited the TLR-4-mediated nuclear factor (NF)-κB signaling pathway. To bolster our findings, in vitro studies demonstrated that amitriptyline downregulated the TLR-4/NF-κB/mitogen-activated protein kinase signaling cascades in mouse macrophages stimulated with lipopolysaccharide. Further molecular investigations revealed that amitriptyline was able to suppress the elevated expression of myeloid differentiation factor 2 that lipopolysaccharide stimulation typically induces. In summary, our findings suggest that amitriptyline effectively mitigates DSS-induced colitis in mice through the inhibition of TLR-4/myeloid differentiation 2 pathway signaling, indicating its potential repurposing for IBD treatment. SIGNIFICANCE STATEMENT: The potential of using amitriptyline in treating inflammatory bowel disease appears promising, leveraging its established safety and dosing profile as an antidepressant. The study results show that amitriptyline can alleviate pathological symptoms, inflammation, and intestinal mucosal damage in mice with colitis induced by DSS. The protective effect observed appears to be linked to the inhibition of TLR-4/myeloid differentiation 2 signaling pathway. By exploring novel applications for existing medications, we can optimize amitriptyline's efficacy and broaden its impact in both medical and commercial contexts.
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Affiliation(s)
- Chengcheng Zeng
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Qingqing Zhu
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Chen Huang
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Huiting Chen
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Hongli Huang
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Yongjian Zhou
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Chong Zhao
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China.
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25
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Chen N, Yao P, Farid MS, Zhang T, Luo Y, Zhao C. Effect of bioactive compounds in processed Camellia sinensis tea on the intestinal barrier. Food Res Int 2025; 199:115383. [PMID: 39658174 DOI: 10.1016/j.foodres.2024.115383] [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: 08/17/2024] [Revised: 10/18/2024] [Accepted: 11/14/2024] [Indexed: 12/12/2024]
Abstract
The human intestinal tract plays a pivotal role in safeguarding the body against noxious substances and microbial pathogens by functioning as a barrier. This barrier function is achieved through the combined action of physical, chemical, microbial, and immune components. Tea (Camellia sinensis) is the most widely consumed beverage in the world, and it is consumed and appreciated in a multitude of regions across the globe. Tea can be classified into various categories, including green, white, yellow, oolong, black, and dark teas, based on the specific processing methods employed. In recent times, there has been a notable surge in scientific investigation into the various types of tea. The recent surge in research on tea can be attributed to the plethora of bioactive compounds it contains, including polyphenols, polysaccharides, pigments, and theanine. The processing of different teas affects the active ingredients to varying degrees, resulting in a range of chemical reactions and the formation of different types and quantities of ingredients. The bioactive compounds present in tea are of great importance for the maintenance of the integrity of the intestinal barrier, operating through a variety of mechanisms. This literature review synthesizes scientific studies on the impact of the primary bioactive compounds and different processing methods of tea on the intestinal barrier function. This review places particular emphasis on the exploration of the barrier repair and regulatory effects of these compounds, including the mitigation of damage to different barriers following intestinal diseases. Specifically, the active ingredients in tea can alleviate damage to physical barriers and chemical barriers by regulating barrier protein expression. At the same time, they can also maintain the stability of immune and biological barriers by regulating the expression of inflammatory factors and the metabolism of intestinal flora. This investigation can establish a strong theoretical foundation for the future development of innovative tea products.
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Affiliation(s)
- Nan Chen
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
| | - Peng Yao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
| | | | - Tiehua Zhang
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
| | - Yangchao Luo
- Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, United States.
| | - Changhui Zhao
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
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26
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Araruna MEC, Alves Júnior EB, de Lima Serafim CA, Pessoa MMB, de Souza Pessôa ML, Alves VP, Sobral MV, da Silva MS, Alves AF, de Paiva Sousa MC, Araújo AA, Batista LM. (-)-Fenchone Ameliorates TNBS-Induced Colitis in Rats via Antioxidant, Immunomodulatory, and Cytoprotective Mechanisms. Pharmaceuticals (Basel) 2024; 18:18. [PMID: 39861081 PMCID: PMC11769309 DOI: 10.3390/ph18010018] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 09/12/2024] [Accepted: 09/16/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND (-)-Fenchone is a bicyclic monoterpene present in the plant species Foeniculum vulgare Mill, Thuja occidentalis L. (tuja), and Lavandula stoechas (lavender). These plants have therapeutic value in the treatment of intestinal disorders. AIM To evaluate intestinal anti-inflammatory activity in an acute and chronic trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. METHODS Intestinal anti-inflammatory effects were assessed using the acute and chronic TNBS-induced colitis model in rats. The mechanisms were evaluated from colonic tissue fragments of the acute and chronic models. RESULTS Oral administration of the (-)-fenchone (37.5-300 mg/kg) acute phase or (150 mg/kg) (p < 0.001) chronic phase reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. At a dose of 150 mg/kg, the acute and chronic phase decreased malondialdehyde (MDA) and myeloperoxidase (MPO) (p < 0.001), restored glutathione (GSH) levels and superoxide dismutase (SOD) (p < 0.001), decreased immunomarking for factor nuclear kappa B (NF-κB) and levels of interleukin (IL)-1 and tumor necrosis factor α (TNF-α), and maintained IL-10 and TGF-β basal levels. Furthermore, increased immunostaining for zonula occludens 1 (ZO-1) was observed. CONCLUSIONS (-)-fenchone has intestinal anti-inflammatory activity related to cytoprotection of the intestinal barrier, as well as antioxidant and immunomodulatory effects.
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Affiliation(s)
- Maria Elaine Cristina Araruna
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Edvaldo Balbino Alves Júnior
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Catarina Alves de Lima Serafim
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Matheus Marley Bezerra Pessoa
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Michelle Liz de Souza Pessôa
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Vitória Pereira Alves
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Marianna Vieira Sobral
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Marcelo Sobral da Silva
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
| | - Adriano Francisco Alves
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
- Department of Physiology and Pathology, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil;
| | - Maria Carolina de Paiva Sousa
- Department of Physiology and Pathology, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil;
| | - Aurigena Antunes Araújo
- Department of Morphology, Histology and Basic Pathology, Biosciences Center, Federal University of Rio Grande do Norte (UFRN), Natal CEP 59078-970, RN, Brazil;
| | - Leônia Maria Batista
- Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa CEP 58051-970, PB, Brazil; (M.E.C.A.); (E.B.A.J.); (C.A.d.L.S.); (M.M.B.P.); (M.L.d.S.P.); (V.P.A.); (M.V.S.); (M.S.d.S.); (A.F.A.)
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Canbolat AA, Lombardo M, Mondragon ADC, López JMM, Bechelany M, Karav S. Bovine Colostrum in Pediatric Nutrition and Health. Nutrients 2024; 16:4305. [PMID: 39770926 PMCID: PMC11677144 DOI: 10.3390/nu16244305] [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: 11/11/2024] [Revised: 12/04/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets and support development. Preterm development is crucial, especially in the maturation of essential systems, and from 2010 to 2020, approximately 15% of all premature births occurred at less than 32 weeks of gestation worldwide. This review explores the composition, benefits, and effects of BC on general infants and children, along with preterm infants who require special care, and highlights its role in growth and development. BC is also associated with specific pediatric diseases, including necrotizing enterocolitis (NEC), infectious diarrhea, inflammatory bowel disease (IBD), short-bowel syndrome (SBS), neonatal sepsis, gastrointestinal and respiratory infections, and some minor conditions. This review also discusses the clinical trials regarding these specific conditions which are occasionally encountered in preterm infants. The anti-inflammatory, antimicrobial, immunomodulatory, and antiviral properties of BC are discussed, emphasizing its mechanisms of action. Clinical trials, particularly in humans, provide evidence supporting the inclusion of BC in formulas and diets, although precise standards for age, feeding time, and amounts are needed to ensure safety and efficacy. However, potential adverse effects, such as allergic reactions to caseins and immunoglobulin E, must be considered. More comprehensive clinical trials are necessary to expand the evidence on BC in infant feeding, and glycans, important components of BC, should be further studied for their synergistic effects on pediatric diseases. Ultimately, BC shows promise for pediatric health and should be incorporated into nutritional supplements with caution.
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Affiliation(s)
- Ahmet Alperen Canbolat
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye;
| | - Mauro Lombardo
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di 11 Val Cannuta 247, 00166 Rome, Italy;
| | - Alicia del Carmen Mondragon
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición Bromatología, Universidade de Santiago de Compostela, Campus Terra, 27002 Lugo, Spain; (A.d.C.M.); (J.M.M.L.)
| | - Jose Manuel Miranda López
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición Bromatología, Universidade de Santiago de Compostela, Campus Terra, 27002 Lugo, Spain; (A.d.C.M.); (J.M.M.L.)
| | - Mikhael Bechelany
- Institut Européen des Membranes (IEM), UMR 5635, University Montpellier, ENSCM, CNRS, F-34095 Montpellier, France;
- Functional Materials Group, Gulf University for Science and Technology (GUST), Masjid Al Aqsa Street, Mubarak Al-Abdullah 32093, Kuwait
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17000, Türkiye;
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Wen T, Liu T, Chen H, Liu Q, Shen X, Hu Q. Demethylzeylasteral alleviates inflammation and colitis via dual suppression of NF-κB and STAT3/5 by targeting IKKα/β and JAK2. Int Immunopharmacol 2024; 142:113260. [PMID: 39340986 DOI: 10.1016/j.intimp.2024.113260] [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: 07/15/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 09/30/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is a common inflammatory bowel disease and a risk factor of colorectal cancer. Demethylzeylasteral (DZT), a bioactive component mainly isolated from Tripterygium wilfordii, has been shown to inhibit inflammation and cancer. However, its anti-UC function and molecular mechanisms have not been well characterized. This study aims to explore the therapeutic effect and functional targets of demethylzeylasteral against UC. METHODS RT-qPCR, Western blot and ELISA were used to detect the generation of pro-inflammatory cytokines and chemokines in murine macrophage cells. Luciferase reporter gene, Western blot, pull-down, CETSA, DARTS, and virtual docking were employed to detect the anti-inflammatory targets and molecular mechanisms of demethylzeylasteral. The anti-inflammatory and anti-colitis effects of demethylzeylasteral were further determined in DSS-challenged mice. RESULTS In vitro, demethylzeylasteral inhibited NO and PGE2 production by suppressing the mRNA and protein expression of iNOS and COX-2, and suppressed the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1, CXCL9, and CXCL10 in RAW264.7 macrophages stimulated by LPS/IFNγ. Furthermore, demethylzeylasteral was not only capable of inhibiting IKKα/β-NF-κB activation, but also able to block JAKs-STAT3/5 activation in LPS/INFγ-incubated RAW264.7 cells or DSS-exposed colon tissues of mice. Mechanistically, demethylzeylasteral was found to directly bind to IKKα/β and JAK2 kinases, leading to inactivation of pro-inflammatory signaling cascades and reduced generation of cytokines and chemokines. In vivo, oral administration of demethylzeylasteral significantly attenuated DSS-induced colitis, which was mainly manifested as mitigated symptoms of colitis, colonic mucosal barrier damage, and colonic inflammation. CONCLUSION We demonstrated that demethylzeylasteral alleviated UC pathology by blocking NF-κB and STAT3/5 pathways via targeting IKKα/β and JAK2 kinases, raising the possibility that demethylzeylasteral could act as a candidate for the treatment of UC.
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Affiliation(s)
- Tian Wen
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Ting Liu
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Hongqing Chen
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qi Liu
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
| | - Xiaofei Shen
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Qiongying Hu
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
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29
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Gupta A, Erridge S, Graf V, Kelada M, Bapir L, Jesuraj N, Warner-Levy J, Clarke E, McLachlan K, Coomber R, Rucker JJ, Platt MW, Sodergren MH. UK medical cannabis registry: an updated analysis of clinical outcomes of cannabis-based medicinal products for inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2024; 18:829-838. [PMID: 39689344 DOI: 10.1080/17474124.2024.2443574] [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: 08/28/2024] [Revised: 11/26/2024] [Accepted: 12/13/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Treatments for inflammatory bowel disease (IBD) remain limited, and cannabis-based medicinal products (CBMPs) provide promise in addressing inflammation and pain. However, long-term data on CBMP efficacy in IBD are scarce. This study examines health-related quality of life (HRQoL) changes in IBD patients treated with CBMPs. RESEARCH DESIGN AND METHODS Patients with IBD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the short IBD questionnaire (SIBDQ), EQ-5D-5L, single-item sleep quality scale (SQS), and generalized anxiety disorder-7 (GAD-7), from baseline to 18-months after CBMP treatment started. Secondary outcomes were adverse event prevalence. RESULTS Analysis of 116 patients with IBD included 94 males (81.03%) with a mean age of 39.52 ± 9.12 years. There were improvements in the SIBDQ, GAD-7, SQS, and EQ-5D-5L Index (p < 0.001). At 18-months, 30 (25.86%) patients achieved a minimal clinically important difference (MCID) in the SIBDQ. Patients with severe baseline anxiety and above-median THC doses were more likely to achieve this MCID (p < 0.050). Twenty (17.24%) patients reported 155 (133.62%) adverse events. CONCLUSIONS CBMP treatment was associated with improvement in IBD-specific outcomes in patients and general HRQoL over 18-months. However, causation cannot be inferred. Hence, randomized controlled trials are still required.
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Affiliation(s)
- Aashray Gupta
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Simon Erridge
- Medical Cannabis Research Group, Imperial College London, London, UK
- Department of Medicine, Curaleaf Clinic, London, UK
| | - Vivian Graf
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Monica Kelada
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Lara Bapir
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - Naveen Jesuraj
- Medical Cannabis Research Group, Imperial College London, London, UK
| | - John Warner-Levy
- Medical Cannabis Research Group, Imperial College London, London, UK
| | | | | | - Ross Coomber
- Department of Medicine, Curaleaf Clinic, London, UK
- Department of Trauma and Orthopaedics, St. George's Hospital NHS Trust, London, UK
| | - James J Rucker
- Department of Medicine, Curaleaf Clinic, London, UK
- Department of Psychological Medicine, Kings College London, London, UK
- Centre for Affective Disorders, South London & Maudsley NHS Foundation Trust, London, UK
| | | | - Mikael H Sodergren
- Medical Cannabis Research Group, Imperial College London, London, UK
- Department of Medicine, Curaleaf Clinic, London, UK
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Liu R, Ding X, Dang M, Wang J, Zhu W. Effects of hesperidin, thymol, rosmarinic acid and their combined effect on growth performance, intestinal barrier function and cecal microbiota in broilers. Poult Sci 2024; 103:104247. [PMID: 39265517 PMCID: PMC11416348 DOI: 10.1016/j.psj.2024.104247] [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: 05/20/2024] [Revised: 08/12/2024] [Accepted: 08/18/2024] [Indexed: 09/14/2024] Open
Abstract
This study aims to investigate the effects of hesperidin (Hes), thymol (Thy), rosmarinic acid (RA) and their combined effect on broiler growth performance, intestinal barrier function, and cecal microbiota. A total of 240 newly hatched Arbor Acres broiler chicks were randomly divided into 5 treatments with 6 replicates of 8 chickens. The birds were fed a basal diet (Con group), a basal diet supplemented with 40 mg/kg Hes (Hes group), a basal diet supplemented with 40 mg/kg Thy (Thy group), a basal diet supplemented with 20 mg/kg RA (RA group), or a basal diet supplemented with 40 mg/kg Hes + 40 mg/kg Thy + 20 mg/kg RA (HTR group) for 42 d. The results indicated that dietary Hes and HTR supplementation enhanced average daily gain, final body weight, and eviscerated yield of broilers compared with the Con group (P < 0.05). Notably, the HTR treatment showed a decrease in abdominal fat yield and ratio of feed to weight gain (P < 0.05). HTR treatment increased ileal villus height, villus height/crypt depth, and number of goblet cells, decreased the crypt depth (P < 0.05), up-regulated the mRNA expression of tight junction proteins (ZO-1, Claudin-1, Occludin) and MUC2 (P < 0.05). Hes, Thy, RA, HTR treatment decreased the concentrations of pro-inflammatory factors (IL-8, IFN-γ and TNF-α), and down-regulated the mRNA expression of TLR4/MyD88/NF-κB (P < 0.05). Importantly, the supplementation of HTR increased the relative abundance of beneficial bacteria (Parabacteroides, Lachnosiraceae NK4A136 and Turicbacter) and significantly decreased the relative abundance of opportunistic pathogenic bacteria such as Colidextribacter (P < 0.05). Additionally, the concentrations of propionate and butyrate in the cecum were elevated in the HTR group (P < 0.05). These findings indicate that the diet supplemented with HTR improved the growth performance and intestinal barrier function in broilers by modulating the cecal microbiota and its metabolites.
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Affiliation(s)
- Ruixue Liu
- National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Xuedong Ding
- National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Miaomiao Dang
- National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Jing Wang
- National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | - Weiyun Zhu
- National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
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Cho Y, Sung MH, Kang HT, Lee JH. Establishment of an Apical-Out Organoid Model for Directly Assessing the Function of Postbiotics. J Microbiol Biotechnol 2024; 34:2184-2191. [PMID: 39317684 PMCID: PMC11637808 DOI: 10.4014/jmb.2405.05034] [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: 05/28/2024] [Revised: 08/22/2024] [Accepted: 08/29/2024] [Indexed: 09/26/2024]
Abstract
In vitro organoids that mimic the physiological properties of in vivo organs based on three-dimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.
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Affiliation(s)
- Yeonoh Cho
- Department of Food Science and Biotechnology, College of Bio-Nano Technology, Gachon University, Gyeonggi 13120, Republic of Korea
| | - Moon-Hee Sung
- KookminBio Corporation, Seoul 02826, Republic of Korea
| | - Hee-Taik Kang
- Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jong Hun Lee
- Department of Food Science and Biotechnology, College of Bio-Nano Technology, Gachon University, Gyeonggi 13120, Republic of Korea
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Xu Y, Huang C, Xu H, Xu J, Cheng KW, Mok HL, Lyu C, Zhu L, Lin C, Tan HY, Bian Z. Modified Zhenwu Decoction improved intestinal barrier function of experimental colitis through activation of sGC-mediated cGMP/PKG signaling. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118570. [PMID: 39002824 DOI: 10.1016/j.jep.2024.118570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/13/2024] [Accepted: 07/09/2024] [Indexed: 07/15/2024]
Abstract
BACKGROUND The invasion of luminal antigens and an aberrant immune response resulting from a disrupted physical epithelial barrier are the key characteristics of ulcerative colitis (UC). The restoration of damaged epithelial function is crucial for maintaining mucosal homeostasis and disease quiescence. Current therapies for UC primarily focus on suppressing inflammation. However, most patients fail to respond to therapy or develop secondary resistance over time, emphasizing the need to develop novel therapeutic targets for UC. Our study aimed to identify the potential targets of a novel modified herbal formula from the Zhen Wu Decoction, namely CDD-2103, which has demonstrated promising efficacy in treating chronic colitis. METHODS The effect of CDD-2103 on epithelial barrier function was examined using in vitro and ex vivo models of tissue injury, as well as a chronic colitis C57BL/6 mouse model. Transcriptomic analysis was employed to profile gene expression changes in colonic tissues following treatment with CDD-2103. RESULTS Our in vivo experiments demonstrated that CDD-2103 dose-dependently reduced disease severity in mice with chronic colitis. The efficacy of CDD-2103 was mediated by a reduction in goblet cell loss and the enhancement of tight junction protein integrity. Mechanistically, CDD-2103 suppressed epithelial cell apoptosis and tight junction protein breakdown by activating the soluble guanynyl cyclase (sGC)-mediated cyclic guanosine monophosphate (cGMP)/PKG signaling cascade. Molecular docking analysis revealed strong sGC ligand recognition by the CDD-2103-derived molecules, warranting further investigation. CONCLUSION Our study revealed a novel formulation CDD-2103 that restores intestinal barrier function through the activation of sGC-regulated cGMP/PKG signaling. Furthermore, our findings suggest that targeting sGC can be an effective approach for promoting mucosal healing in the management of UC.
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Affiliation(s)
- Yiqi Xu
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Chunhua Huang
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Hengyue Xu
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China
| | - Jiaruo Xu
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Ka Wing Cheng
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Heung Lam Mok
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Cheng Lyu
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Lin Zhu
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Chengyuan Lin
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China
| | - Hor Yue Tan
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
| | - Zhaoxiang Bian
- Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
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Wu Y, Zhang X, Liu X, Zhao Z, Tao S, Xu Q, Zhao J, Dai Z, Zhang G, Han D, Wang J. Galactooligosaccharides and Limosilactobacillus reuteri synergistically alleviate gut inflammation and barrier dysfunction by enriching Bacteroides acidifaciens for pentadecanoic acid biosynthesis. Nat Commun 2024; 15:9291. [PMID: 39468026 PMCID: PMC11519483 DOI: 10.1038/s41467-024-53144-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 10/01/2024] [Indexed: 10/30/2024] Open
Abstract
Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.
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Affiliation(s)
- Yujun Wu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Xiangyu Zhang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Xiaoyi Liu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Zhenguo Zhao
- Department of General Surgery, Jiangyin People's Hospital Affiliated to Nantong University, Jiangsu, 214400, China
| | - Shiyu Tao
- College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Qian Xu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jinbiao Zhao
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Zhaolai Dai
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Guolong Zhang
- Department of Animal and Food Sciences, Oklahoma State University, Stillwater, 74078, USA
| | - Dandan Han
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
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Zeng X, Wang H, Wu T, Zhou Z, Zhou J, Fu H. Associations of intestinal diseases with anal diseases: a Mendelian randomization study. Sci Rep 2024; 14:24304. [PMID: 39414900 PMCID: PMC11484769 DOI: 10.1038/s41598-024-75082-0] [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: 03/26/2024] [Accepted: 10/01/2024] [Indexed: 10/18/2024] Open
Abstract
Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn's disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.
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Affiliation(s)
- XiaoYu Zeng
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - HanYu Wang
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Ting Wu
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - ZiNing Zhou
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - JianPing Zhou
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Hao Fu
- Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Siti Sarah CO, Mohd Ashari NS. Exploration of Allergic Rhinitis: Epidemiology, Predisposing Factors, Clinical Manifestations, Laboratory Characteristics, and Emerging Pathogenic Mechanisms. Cureus 2024; 16:e71409. [PMID: 39539885 PMCID: PMC11558229 DOI: 10.7759/cureus.71409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2024] [Indexed: 11/16/2024] Open
Abstract
Allergic rhinitis (AR) is a widespread allergic condition, with its prevalence continuing to rise globally. This disease has a significant impact on patients' quality of life. Understanding the underlying pathophysiology is important to develop better-targeted therapies. For decades, the primary assumption has been that an allergy is caused by unbalanced and overactive immunological responses against allergens, driven mainly by activated T helper 2 (Th2) cells and due to aberrant T-regulatory cells. The more recent hypothesis that is gaining attention relies on the dysregulation of the epithelial barrier, which might result in allergen uptake as a primary defect in the pathogenesis of allergic reactions. The nasal epithelial barrier is considered a crucial first line of defense in the upper airway, as it protects the host's immune system from exposure to allergens. Thus, this review will discuss AR's epidemiology, predisposing factors, clinical manifestations, laboratory characteristics, and pathogenic mechanisms.
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Affiliation(s)
- Che Othman Siti Sarah
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MYS
| | - Noor Suryani Mohd Ashari
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MYS
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Markus V. Gut bacterial quorum sensing molecules and their association with inflammatory bowel disease: Advances and future perspectives. Biochem Biophys Res Commun 2024; 724:150243. [PMID: 38857558 DOI: 10.1016/j.bbrc.2024.150243] [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: 03/07/2024] [Revised: 05/15/2024] [Accepted: 06/06/2024] [Indexed: 06/12/2024]
Abstract
Inflammatory Bowel Disease (IBD) is an enduring inflammatory disease of the gastrointestinal tract (GIT). The complexity of IBD, its profound impact on patient's quality of life, and its burden on healthcare systems necessitate continuing studies to elucidate its etiology, refine care strategies, improve treatment outcomes, and identify potential targets for novel therapeutic interventions. The discovery of a connection between IBD and gut bacterial quorum sensing (QS) molecules has opened exciting opportunities for research into IBD pathophysiology. QS molecules are small chemical messengers synthesized and released by bacteria based on population density. These chemicals are sensed not only by the microbial species but also by host cells and are essential in gut homeostasis. QS molecules are now known to interact with inflammatory pathways, therefore rendering them potential therapeutic targets for IBD management. Given these intriguing developments, the most recent research findings in this area are herein reviewed. First, the global burden of IBD and the disruptions of the gut microbiota and intestinal barrier associated with the disease are assessed. Next, the general QS mechanism and signaling molecules in the gut are discussed. Then, the roles of QS molecules and their connection with IBD are elucidated. Lastly, the review proposes potential QS-based therapeutic targets for IBD, offering insights into the future research trajectory in this field.
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Affiliation(s)
- Victor Markus
- Near East University, Faculty of Medicine, Department of Medical Biochemistry, Nicosia, TRNC Mersin 10, Turkey.
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Severino A, Tohumcu E, Tamai L, Dargenio P, Porcari S, Rondinella D, Venturini I, Maida M, Gasbarrini A, Cammarota G, Ianiro G. The microbiome-driven impact of western diet in the development of noncommunicable chronic disorders. Best Pract Res Clin Gastroenterol 2024; 72:101923. [PMID: 39645277 DOI: 10.1016/j.bpg.2024.101923] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 05/02/2024] [Indexed: 07/23/2024]
Abstract
Noncommunicable chronic disorders (NCDs) are multifactorial disorders that share a state of chronic, low-grade inflammation together with an imbalance of gut microbiota. NCDs are becoming increasingly prevalent worldwide, and mainly in Western countries, with a significant impact on global health. Societal changes, together with the widespread diffusion of modern agricultural methods and food processing, have led to a significant shift in dietary habits over the past century, with an increased diffusion of the Western diet (WD). WD includes foods high in saturated fat, refined sugars, salt, sweeteners, and low in fiber, and is characterized by overeating, frequent snacking, and a prolonged postprandial state. An increasing body of evidence supports the association between the diffusion of WD and the rising prevalence of NCDs. WD also negatively affects both gut microbiota and the immune system by driving to microbial alterations, gut barrier dysfunction, increased intestinal permeability, and leakage of harmful bacterial metabolites into the bloodstream, with consequent contribution to the development of systemic low-grade inflammation. In this review article we aim to dissect the role of gut microbiota imbalance and gut barrier impairment in mediating the detrimental effects of WD on the development of NCDs, and to identify potential therapeutic strategies.
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Affiliation(s)
- Andrea Severino
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
| | - Ege Tohumcu
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Luca Tamai
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Pasquale Dargenio
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Serena Porcari
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Debora Rondinella
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Irene Venturini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Marcello Maida
- Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
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Li W, Tang X, Liu H, Liu K, Tian Z, Zhao Y. Protective effect of 1,3-dioleoyl-2-palmitoylglycerol against DSS-induced colitis via modulating gut microbiota and maintaining intestinal epithelial barrier integrity. Food Funct 2024; 15:8700-8711. [PMID: 39076044 DOI: 10.1039/d4fo02344g] [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: 07/31/2024]
Abstract
Inflammatory bowel disease (IBD) is a challenging condition to cure that can occur at any age. The gut microbiome and intestinal epithelial barrier play a crucial role in the development of IBD. 1,3-Dioleoyl-2-palmitoylglycerol (OPO), the predominant triglyceride in breast milk, is a structural lipid with multiple physiological functions. However, the protective effect of OPO on IBD and its underlying mechanism remains unclear. This study showed that oral administration of OPO markedly ameliorated dextran sulfate sodium (DSS)-induced colitis phenotypes. OPO treatment reduced inflammation levels by suppressing the TLR4-MyD88-NF-κB signaling pathway in colitis mice. Furthermore, OPO treatment improved intestinal epithelial barrier function via promoting epithelial cell proliferation and differentiation, inhibiting cell apoptosis, and upregulating tight junction protein expression. The 16S rRNA gene sequencing revealed that OPO treatment restored microbial alpha diversity and reshaped the microbiota of colitis mice. Therefore, our study revealed that OPO exhibited a protective role in DSS-induced colitis via maintaining intestinal epithelial barrier integrity and modulating gut microbiota. Our results highlight that OPO could be used as effective supplements for individuals with IBD or intestinal dysfunctions.
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Affiliation(s)
- Wusun Li
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Xiaoyan Tang
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Hui Liu
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Ke Liu
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Zhiqing Tian
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Yujie Zhao
- Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards & Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
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Yip JLK, Balasuriya GK, Hill-Yardin EL, Spencer SJ. The gut-brain and gut-macrophage contribution to gastrointestinal dysfunction with systemic inflammation. Brain Behav Immun 2024; 119:867-877. [PMID: 38750700 DOI: 10.1016/j.bbi.2024.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/24/2024] [Accepted: 05/12/2024] [Indexed: 05/19/2024] Open
Abstract
The gastrointestinal tract is one of the main organs affected during systemic inflammation and disrupted gastrointestinal motility is a major clinical manifestation. Many studies have investigated the involvement of neuroimmune interactions in regulating colonic motility during localized colonic inflammation, i.e., colitis. However, little is known about how the enteric nervous system and intestinal macrophages contribute to dysregulated motility during systemic inflammation. Given that systemic inflammation commonly results from the innate immune response against bacterial infection, we mimicked bacterial infection by administering lipopolysaccharide (LPS) to rats and assessed colonic motility using ex vivo video imaging techniques. We utilized the Cx3cr1-Dtr rat model of transient depletion of macrophages to investigate the role of intestinal macrophages in regulating colonic motility during LPS infection. To investigate the role of inhibitory enteric neurotransmission on colonic motility following LPS, we applied the nitric oxide synthase inhibitor, Nω-nitro-L-arginine (NOLA). Our results confirmed an increase in colonic contraction frequency during LPS-induced systemic inflammation. However, neither the depletion of intestinal macrophages, nor the suppression of inhibitory enteric nervous system activity impacted colonic motility disruption during inflammation. This implies that the interplay between the enteric nervous system and intestinal macrophages is nuanced, and complex, and further investigation is needed to clarify their joint roles in colonic motility.
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Affiliation(s)
- Jackson L K Yip
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
| | - Gayathri K Balasuriya
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia; Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan
| | - Elisa L Hill-Yardin
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia
| | - Sarah J Spencer
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC, Australia.
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40
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Yang Y, Zhao C, Yang Z, Du C, Chang Z, Wen X, Zhang X, Liu Y, Hu L, Gao Z. Myeloid-derived growth factor ameliorates dextran sodium sulfate-induced colitis by regulating macrophage polarization. J Mol Med (Berl) 2024; 102:875-886. [PMID: 38695882 PMCID: PMC11213757 DOI: 10.1007/s00109-024-02447-3] [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: 10/10/2023] [Revised: 03/19/2024] [Accepted: 04/15/2024] [Indexed: 06/29/2024]
Abstract
Inflammatory bowel disease (IBD) is characterized by inflammatory conditions in the gastrointestinal tract. According to reports, IBD prevalence is increasing globally, with heavy economic and physical burdens. Current IBD clinical treatment is limited to pharmacological methods; therefore, new strategies are needed. Myeloid-derived growth factor (MYDGF) secreted by bone marrow-derived mononuclear macrophages has beneficial effects in multiple inflammatory diseases. To this end, the present study aimed to establish an experimental IBD mouse model using dextran sulfate sodium in drinking water. MYDGF significantly alleviated DSS-induced colitis, suppressed lymphocyte infiltration, restored epithelial integrity in mice, and decreased apoptosis in the colon tissue. Moreover, the number of M1 macrophages was decreased and that of M2 macrophages was increased by the action of MYDGF. In MYDGF-treated mice, the NF-κB and MAPK pathways were partially inhibited. Our findings indicate that MYDGF could mitigate DSS-induced mice IBD by reducing inflammation and restoring epithelial integrity through regulation of intestinal macrophage polarization via NF-κB and MAPK pathway inhibition. KEY MESSAGES: MYDGF alleviated DSS-induced acute colitis. MYDGF maintains colon epithelial barrier integrity and relieves inflammation. MYDGF regulates colon macrophage polarization. MYDGF partially inhibited the activation of NF-κB and MAPK pathway.
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Affiliation(s)
- Yang Yang
- Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China
| | - Conghui Zhao
- Department of Pathology, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China
| | - Zi Yang
- Department of Endodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China
| | - Conglin Du
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology and Beijing Laboratory of Oral Health, Beijing, 100050, China
| | - Zhichao Chang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology and Beijing Laboratory of Oral Health, Beijing, 100050, China
| | - Xin Wen
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology and Beijing Laboratory of Oral Health, Beijing, 100050, China
| | - Xiujuan Zhang
- Nephrology Department, Zhucheng People's Hospital, Shandong, 262200, China
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, China.
| | - Liang Hu
- Department of Oral and Maxillofacial Surgery, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China.
| | - Zhenhua Gao
- Department of Oral and Maxillofacial Surgery, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China.
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Tang X, Chen X, Ferrari M, Walvoort MTC, de Vos P. Gut Epithelial Barrier Function is Impacted by Hyperglycemia and Secondary Bile Acids in Vitro: Possible Rescuing Effects of Specific Pectins. Mol Nutr Food Res 2024; 68:e2300910. [PMID: 38794856 DOI: 10.1002/mnfr.202300910] [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: 12/22/2023] [Revised: 04/24/2024] [Indexed: 05/26/2024]
Abstract
Gut epithelial barrier disruption is commonly observed in Western diseases like diabetes and inflammatory bowel disease (IBD). Enhanced epithelial permeability triggers inflammatory responses and gut microbiota dysbiosis. Reduced bacterial diversity in IBD affects gut microbiota metabolism, altering microbial products such as secondary bile acids (BAs), which potentially play a role in gut barrier regulation and immunity. Dietary fibers such as pectin may substitute effects of these BAs. The study examines transepithelial electrical resistance of gut epithelial T84 cells and the gene expression of tight junctions after exposure to (un)sulfated secondary BAs. This is compared to the impact of the dietary fiber pectin with different degrees of methylation (DM) and blockiness (DB), with disruption induced by calcium ionophore A23187 under both normal and hyperglycemic conditions. Unsulfated lithocholic acid (LCA) and deoxycholic acid (DCA) show a stronger rescuing effect, particularly evident under 20 mM glucose levels. DM19 with high DB (HB) and DM43HB pectin exhibit rescuing effects under both glucose conditions. Notably, DM19HB and DM43HB display higher rescue effects under 20 mM glucose compared to 5 mM glucose. The study demonstrates that specific pectins such as DM19HB and DM43HB may serve as alternatives for preventing barrier disruption in the case of disturbed DCA metabolism.
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Affiliation(s)
- Xin Tang
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
| | - Xiaochen Chen
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
| | - Michela Ferrari
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Marthe T C Walvoort
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Paul de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
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Oliveira ICCS, Marinsek GP, Correia LVB, da Silva RCB, Castro IB, Mari RB. Tributyltin (TBT) toxicity: Effects on enteric neuronal plasticity and intestinal barrier of rats' duodenum. Auton Neurosci 2024; 253:103176. [PMID: 38669866 DOI: 10.1016/j.autneu.2024.103176] [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: 10/20/2023] [Revised: 03/20/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024]
Abstract
Tributyltin (TBT) is a biocide used in the formulation of antifouling paints and it is highly harmful. Despite the ban, the compound persists in the environment, contaminating marine foodstuffs and household products. Therefore, considering the route of exposure to the contaminant, the gastrointestinal tract (GIT) acts as an important barrier against harmful substances and is a potential biomarker for understanding the consequences of these agents. This work aimed to evaluate histological and neuronal alterations in the duodenum of male Wistar rats that received 20 ng/g TBT and 600 ng/g via gavage for 30 consecutive days. After the experimental period, the animals were euthanized, and the duodenum was intended for neuronal histochemistry (total and metabolically active populations) and histological routine (morphometry and histopathology). The results showed more severe changes in neuronal density and intestinal morphometry in rats exposed to 20 ng/g, such as total neuronal density decrease and reduction of intestinal layers. In rats exposed to 600 ng/g of TBT, it was possible to observe only an increase in intraepithelial lymphocytes. We conclude that TBT can be more harmful to intestinal homeostasis when consumed in lower concentrations.
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Affiliation(s)
- I C C S Oliveira
- UNESP- São Paulo State University, Institute of Biosciences, Paulista Coast Campus (CLP), São Vicente, SP, Brazil.
| | - G P Marinsek
- UNESP- São Paulo State University, Institute of Biosciences, Paulista Coast Campus (CLP), São Vicente, SP, Brazil.
| | - L V B Correia
- UNIFESP- Federal University of São Paulo, Institute of Health and Society, Baixada Santista Campus, Santos, SP, Brazil
| | - R C B da Silva
- UNIFESP- Federal University of São Paulo, Institute of Health and Society, Baixada Santista Campus, Santos, SP, Brazil
| | - I B Castro
- UNIFESP- Federal University of São Paulo, Institute of Marine Science, Baixada Santista Campus, Santos, SP, Brazil.
| | - R B Mari
- UNESP- São Paulo State University, Institute of Biosciences, Paulista Coast Campus (CLP), São Vicente, SP, Brazil.
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Yang MJ, Zhang YN, Qiao Z, Xu RY, Chen SM, Hu P, Yu HL, Pan Y, Cao J. An investigation into the HIF-dependent intestinal barrier protective mechanism of Qingchang Wenzhong decoction in ulcerative colitis management. JOURNAL OF ETHNOPHARMACOLOGY 2024; 325:117807. [PMID: 38280661 DOI: 10.1016/j.jep.2024.117807] [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: 12/09/2023] [Revised: 01/15/2024] [Accepted: 01/19/2024] [Indexed: 01/29/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease affecting the colon and rectum with an etiology that remains elusive. Traditional Chinese medicine (TCM) has been widely used on long-term UC treatment to better maintain the efficacy than traditional aminosalicylic acid or glucocorticosteroids and to ease financial burden of patients. Qingchang Wenzhong Decoction (QCWZD) is a modern TCM decoction with established clinical efficacy but the mechanism of its protection on intestinal barrier function remains unclear. AIM OF THE STUDY Current findings highlight that the activation of the hypoxia inducible factor (HIF) pathway can facilitate the repair of intestinal epithelium barrier. This study is to investigate the protective effects of QCWZD and its HIF-targeted ingredients on hypoxia-dependent intestinal barrier. METHODS The mice model of UC was induced by dextran sulfate sodium (DSS). Disease activity index (DAI) and histopathology scores and colon length were used to measure the severity of colitis. The DAO activity in serum and protein expression of tight junction (TJ) proteins were detected to explore the function of intestinal barrier. The protein levels of HIF-1α and its downstream gene heme oxygenase-1 (HO-1) were measured as well. HIF-targeted active ingredients in QCWZD were selected by network pharmacology and molecular docking. Protective effects of six constituents on HIF-related anti-oxidative and barrier protective pathway were evaluated by lipopolysaccharide (LPS)-induced HT29 and RAW264.7 cells, through the measurement of the production of ROS and mRNA level of pro-inflammatory cytokines. HIF-1α knockdown was carried out to explore the correlation of protection effects with HIF-related pathway of the active ingredients. RESULTS QCWZD effectively alleviated colitis induced by DSS and demonstrated a protective effect on intestinal barrier function by upregulating HIF-related pathways. Six specific ingredients in QCWZD, targeting HIF, successfully reduced the production of cellular ROS and proinflammatory cytokines in LPS-induced cells. It is noteworthy that the barrier protection provided by these molecules is intricately linked with the HIF-related pathway. CONCLUSIONS This study elucidates the HIF-related molecular mechanism of QCWZD in protecting the function of the epithelial barrier. Six compounds targeting the activation of the HIF-dependent pathway were demonstrated to unveil a novel therapeutic approach for managing UC.
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Affiliation(s)
- Meng-Juan Yang
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Yi-Nuo Zhang
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Zhi Qiao
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Rui-Ying Xu
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Si-Min Chen
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Po Hu
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Hong-Li Yu
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
| | - Yang Pan
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
| | - Jing Cao
- School of pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
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Li Q, Li J, Yin L, Huang J, Liu X, Shi J, Geng Z, Song X, Wang L, Wang Y, Zhang X, Zuo L, Hu J. Sophoricoside improved Crohn's disease-like colitis by inhibiting intestinal epithelial cell apoptosis through PI3K/AKT signaling. Int Immunopharmacol 2024; 131:111886. [PMID: 38493691 DOI: 10.1016/j.intimp.2024.111886] [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: 01/23/2024] [Revised: 03/05/2024] [Accepted: 03/13/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND AND AIMS Increased apoptosis of intestinal epithelial cells (IECs) is a significant cause of intestinal barrier dysfunction in Crohn's disease (CD). Sophoricoside (SOP) is an isoflavone glycoside known for its anti-apoptotic properties. The aim of this study was to investigate the effects of SOP on mice with CD-like colitis and to understand the underlying mechanisms. METHODS Mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to examine the therapeutic effect of SOP on CD-like colitis and intestinal barrier damage. To further explore SOP's impact on IECs apoptosis and intestinal barrier protection, an in vitro colonic organoid apoptosis model induced by TNF-α was utilized. Network pharmacology was employed to predict the relevant pathways and molecular processes associated with SOP in the treatment of CD. RESULTS Treatment with SOP significantly improved colitis symptoms in TNBS mice, as demonstrated by reductions in the Disease Activity Index (DAI), weight loss, colon shortening, macroscopic scores, colonic tissue inflammatory scores, and the expression of pro-inflammatory factors. Our experiments confirmed that SOP protects the intestinal barrier by counteracting IECs apoptosis. Additionally, this study established that SOP reduced IECs apoptosis by inhibiting the PI3K/AKT signaling pathway. CONCLUSIONS SOP can reduce IECs apoptosis through the inhibition of the PI3K/AKT signaling pathway, thereby protecting the intestinal barrier. This study is the first to illustrate how SOP ameliorates colitis and protects the intestinal barrier, suggesting SOP has potential clinical application in treating CD.
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Affiliation(s)
- Qingqing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China
| | - Jing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Lixia Yin
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China
| | - Ju Huang
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China
| | - Xinyue Liu
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China
| | - Jinran Shi
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China
| | - Zhijun Geng
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Xue Song
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Lian Wang
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Yueyue Wang
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Xiaofeng Zhang
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Lugen Zuo
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Jianguo Hu
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, Anhui, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
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Jayaprakash J, B. Gowda SG, K. Shukla P, Gowda D, Nath LR, Chiba H, Rao R, Hui SP. Sex-Specific Effect of Ethanol on Colon Content Lipidome in a Mice Model Using Nontargeted LC/MS. ACS OMEGA 2024; 9:16044-16054. [PMID: 38617688 PMCID: PMC11007720 DOI: 10.1021/acsomega.3c09597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 02/15/2024] [Accepted: 03/18/2024] [Indexed: 04/16/2024]
Abstract
Consumption of alcohol has widespread effects on the human body. The organs that are most significantly impacted are the liver and digestive system. When alcohol is consumed, it is absorbed in the intestines and processed by the liver. However, excessive alcohol use may affect gut epithelial integrity, microbiome composition, and lipid metabolism. Despite past studies investigating the effect of ethanol on hepatic lipid metabolism, the focus on colonic lipid metabolism has not been well explored. In this study, we investigated the sex-specific effect of ethanol on the colonic content lipidome in a mouse model using nontargeted liquid chromatography-mass spectrometry. Comprehensive lipidome analysis of colonic flush samples was performed using ethanol-fed (EF) and pair-fed (PF) mice of each sex. Partial least-squares discriminant analysis revealed that ethanol altered colonic lipid composition largely in male mice compared with female mice. A significant increase in free fatty acids, ceramides, and hexosylceramides and decreased phosphatidylglycerols (PG) was observed in the EF group compared to the PF group in male mice. Phosphatidylethanolamine (PE) levels were increased significantly in the EF group of both sexes compared to the PF group. The volcanic plot shows that PG (O-15:1/15:0) and PE (O-18:2/15:0) are common markers that are increased in both sexes of the EF group. In addition, decreased fatty acid esters of hydroxy fatty acids (FAHFA) were observed specifically in the EF group of female mice. Overall, a significant variation in the mice colonic content lipidome between the EF and PF groups was observed. Target pathways, such as sphingolipid metabolism in males, FAHFA in females, and PE metabolism in both sexes, were suggested. This study provides new insight into the sex-dependent lipid change associated with alcohol-induced gut-microbiota dysfunction and its potential health impacts.
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Affiliation(s)
- Jayashankar Jayaprakash
- Graduate
School of Global Food Resources, Hokkaido
University, Kita-9, Nishi-9, Kita-Ku, Sapporo 060-0809, Japan
| | - Siddabasave Gowda B. Gowda
- Graduate
School of Global Food Resources, Hokkaido
University, Kita-9, Nishi-9, Kita-Ku, Sapporo 060-0809, Japan
- Faculty
of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan
| | - Pradeep K. Shukla
- Department
of Physiology, College of Medicine, University
of Tennessee Health Science Center, 19 S Manassas, Memphis, Tennessee 38163, United States
| | - Divyavani Gowda
- Faculty
of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan
| | - Lipsa Rani Nath
- Graduate
School of Global Food Resources, Hokkaido
University, Kita-9, Nishi-9, Kita-Ku, Sapporo 060-0809, Japan
| | - Hitoshi Chiba
- Department
of Nutrition, Sapporo University of Health
Sciences, Nakanuma, Nishi-4-3-1-15, Higashi-ku, Sapporo 007-0894, Japan
| | - Radhakrishna Rao
- Department
of Physiology, College of Medicine, University
of Tennessee Health Science Center, 19 S Manassas, Memphis, Tennessee 38163, United States
| | - Shu-Ping Hui
- Faculty
of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan
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Yu S, Xie J, Guo Q, Yan X, Wang Y, Leng T, Li L, Zhou J, Zhang W, Su X. Clostridium butyricum isolated from giant panda can attenuate dextran sodium sulfate-induced colitis in mice. Front Microbiol 2024; 15:1361945. [PMID: 38646621 PMCID: PMC11027743 DOI: 10.3389/fmicb.2024.1361945] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/14/2024] [Indexed: 04/23/2024] Open
Abstract
Objective Probiotics are beneficial to the intestinal barrier, but few studies have investigated probiotics from giant pandas. This study aims to explore the preventive effects of giant panda-derived Clostridium butyricum on dextran sodium sulfate (DSS)-induced colitis in mice. Methods Clostridium butyricum was administered to mice 14 days before administering DSS treatment to induce enteritis. Results Clostridium butyricum B14 could more effectively prevent colitis in mice than C. butyricum B13. C. butyricum B14 protected the mouse colon by decreasing the histology index and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, which improved intestinal inflammation-related symptoms. In addition, the treatment led to the regulation of the expression of Tifa, Igkv12-89, and Nr1d1, which in turn inhibited immune pathways. The expression of Muc4, Lama3, Cldn4, Cldn3, Ocln, Zo1, Zo2, and Snai is related the intestinal mucosal barrier. 16S sequencing shows that the C. butyricum B14 significantly increased the abundance of certain intestinal probiotics. Overall, C. butyricum B14 exerted a preventive effect on colitis in mice by inhibiting immune responses, enhancing the intestinal barrier and increasing the abundance of probiotic species. Thus, C. butyricum B14 administration helps regulate the balance of the intestinal microecology. It can suppress immune pathways and enhance barrier-protective proteins.
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Affiliation(s)
- Shuran Yu
- College of Life Science, Southwest Forestry University, Kunming, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu, China
- College of Life Science and Biotechnology, Mianyang Normal University, Mianyang, China
| | - Junjin Xie
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu, China
| | - Qiang Guo
- College of Biodiversity Conservation, Southwest Forestry University, Kunming, China
| | - Xia Yan
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu, China
| | - Yuxiang Wang
- College of Life Science, Southwest Forestry University, Kunming, China
| | - Tangjian Leng
- College of Life Science, Southwest Forestry University, Kunming, China
| | - Lin Li
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu, China
| | - Jielong Zhou
- College of Life Science, Southwest Forestry University, Kunming, China
| | - Wenping Zhang
- College of Life Science and Biotechnology, Mianyang Normal University, Mianyang, China
| | - Xiaoyan Su
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu, China
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47
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Moutusy SI, Ohsako S. Gut Microbiome-Related Anti-Inflammatory Effects of Aryl Hydrocarbon Receptor Activation on Inflammatory Bowel Disease. Int J Mol Sci 2024; 25:3372. [PMID: 38542367 PMCID: PMC10970487 DOI: 10.3390/ijms25063372] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/11/2024] [Accepted: 03/15/2024] [Indexed: 01/05/2025] Open
Abstract
Inflammatory bowel disease (IBD) is one of the most prevalent chronic inflammations of the gastrointestinal tract (GIT). The gut microbial population, the cytokine milieu, the aryl hydrocarbon receptor (AHR) expressed by immune and nonimmune cells and the intrinsic pathway of Th-cell differentiation are implicated in the immunopathology of IBD. AHR activation requires a delicate balance between regulatory and effector T-cells; loss of this balance can cause local gut microbial dysbiosis and intestinal inflammation. Thus, the study of the gut microbiome in association with AHR provides critical insights into IBD pathogenesis and interventions. This review will focus on the recent advancements to form conceptional frameworks on the benefits of AHR activation by commensal gut bacteria in IBD.
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Affiliation(s)
- Salvinaz Islam Moutusy
- Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan;
- Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA
- VA Palo Alto Health Care System, Palo Alto, CA 94305, USA
| | - Seiichiroh Ohsako
- Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan;
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48
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Acciarino A, Diwakarla S, Handreck J, Bergola C, Sahakian L, McQuade RM. The role of the gastrointestinal barrier in obesity-associated systemic inflammation. Obes Rev 2024; 25:e13673. [PMID: 38111141 DOI: 10.1111/obr.13673] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 10/05/2023] [Accepted: 10/27/2023] [Indexed: 12/20/2023]
Abstract
Systemic inflammation is a key contributor to the onset and progression of several obesity-associated diseases and is thought to predominantly arise from the hyperplasia and hypertrophy of white adipose tissue. However, a growing body of works suggests that early changes in the gastrointestinal (GI) barrier may contribute to both local, within the GI lining, and systemic inflammation in obesity. Intestinal barrier dysfunction is well-characterized in inflammatory GI disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and is known to contribute to systemic inflammation. Thus, drawing parallels between GI disorders, where intestinal permeability and systemic inflammation are prominent features, and obesity-induced GI manifestations may provide insights into the potential role of the intestinal barrier in systemic inflammation in obesity. This review summarizes the current literature surrounding intestinal barrier dysfunction in obesity and explores the potential role of intestinal hyperpermeability and intestinal barrier dysfunction in the development of systemic inflammation and GI dysfunction in obesity.
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Affiliation(s)
- Adriana Acciarino
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Shanti Diwakarla
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Jessica Handreck
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Cedrick Bergola
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Lauren Sahakian
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Rachel M McQuade
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Melbourne University, Melbourne, Victoria, Australia
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49
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Li X, Ji LJ, Feng KD, Huang H, Liang MR, Cheng SJ, Meng XD. Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome. World J Gastroenterol 2024; 30:527-541. [PMID: 38463022 PMCID: PMC10921143 DOI: 10.3748/wjg.v30.i6.527] [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: 10/22/2023] [Revised: 11/21/2023] [Accepted: 01/09/2024] [Indexed: 02/05/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease. Despite ongoing advances in our understanding of UC, its pathogenesis is yet unelucidated, underscoring the urgent need for novel treatment strategies for patients with UC. Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules, such as proteins, RNAs, DNA, and metabolites. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, triggering the inflammatory response to a pathogenic agent or injury. Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome, with vital roles in the pathological process of UC. Here, recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC. First, the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized. Finally, an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are highlighted.
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Affiliation(s)
- Xin Li
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou Province, China
| | - Li-Jiang Ji
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, China
| | - Kai-Di Feng
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Hua Huang
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, China
| | - Mei-Rou Liang
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shi-Jin Cheng
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiu-Dong Meng
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou Province, China
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50
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Han SH, Lee HD, Lee S, Lee AY. Taraxacum coreanum Nakai extract attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier dysfunction in Caco-2 cells. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117105. [PMID: 37660957 DOI: 10.1016/j.jep.2023.117105] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/27/2023] [Accepted: 08/28/2023] [Indexed: 09/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Taraxacum coreanum Nakai (TC) is a dandelion native to Korea that has long been used as a medicinal herb with antioxidant and anti-inflammatory properties. Intestinal inflammation is closely associated with intestinal epithelial barrier disruption, which leads to the progression of various intestinal diseases. AIM OF THE STUDY The aim of this study was to investigate the protective effects of TC extract on inflammatory responses and intestinal barrier dysfunction in lipopolysaccharide (LPS)-stimulated Caco-2 cells. MATERIALS AND METHODS The inhibitory effect of TC on nitric oxide (NO) and pro-inflammatory cytokines production were determined by Griess reagent and enzyme-linked immunosorbent assay, respectively. The epithelial permeability was evaluated by transepithelial electrical resistance (TEER) assay, and inflammation- and tight junction (TJ)-related protein expression were analyzed by Western blotting. In addition, the presence of ten active compounds was identified and quantified using UHPLC-ESI-MS and HPLC-DAD analyses. RESULTS Treatment with TC significantly reduced NO production and pro-inflammatory cytokines production [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] compared to the group treated with LPS only, particularly at 100 μg/mL. TC significantly decreased monolayer permeability as detected by TEER. In addition, the transmission of fluorescein isothiocyanate-dextran 4 across the barrier was decreased after treatment with TC. Inflammation-related proteins (inducible NO synthase, cyclooxygenase-2, TNF-α, IL-6, and IL-1β) were down-regulated after treatment with TC. In contrast, TC significantly increased the protein levels of the TJ-related protein, claudin-5. Ten phytochemicals (protocatechuic acid, chlorogenic acid, caffeic acid, scopoletin, chicoric acid, hyperoside, nicotiflorin, luteoloside, sophoricoside, and luteolin) were identified by UHPLC-ESI-MS and HPLC-DAD analysis. CONCLUSION Our findings suggest that ethanolic extract of TC could attenuate the LPS-induced intestinal barrier dysfunction by increasing the TJ protein and suppressing inflammatory responses.
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Affiliation(s)
- Seok Hee Han
- Department of Food Science, Gyeongsang National University, Jinju, 52725, Republic of Korea.
| | - Hak-Dong Lee
- Department of Plant Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea.
| | - Sanghyun Lee
- Department of Plant Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea; Natural Product Institute of Science and Technology, Anseong, 17546, Republic of Korea.
| | - Ah Young Lee
- Department of Food Science, Gyeongsang National University, Jinju, 52725, Republic of Korea.
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