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Chen Y, Wang Y, Shaoyong W, He Y, Liu Y, Wei S, Gan Y, Sun L, Wang Y, Zong X, Xiang Y, Wang Y, Jin M. High-fertility sows reshape gut microbiota: the rise of serotonin-related bacteria and its impact on sustaining reproductive performance. J Anim Sci Biotechnol 2025; 16:73. [PMID: 40400039 PMCID: PMC12096716 DOI: 10.1186/s40104-025-01191-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 03/05/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND Compelling evidence has established a strong link between the gut microbiota and host reproductive health. However, the specific regulatory roles of individual bacterial species on reproductive performance are not well-understood. In the present study, Jinhua sows with varying reproductive performances under the same diet and management conditions were selected to explore potential mechanisms on the intricate relationship between the gut microbiome and host reproductive performance using 16S rRNA sequencing, metagenomics and serum metabolomics. RESULTS Our findings revealed that the KEGG pathways for base excision repair and DNA replication were enriched, along with gene-level enhancements in spore formation, in sows with higher reproductive performance, indicating that the gut microbiome experiences stress. Further analysis showed a positive correlation between these changes and litter size, indicating that the host acts as a stressor, reshaping the microbiome. This adaptation allows the intestinal microbes in sows with high reproductive performance to enrich specific serotonin-related bacteria, such as Oxalobacter formigenes, Ruminococcus sp. CAG 382, Clostridium leptum, and Clostridium botulinum. Subsequently, the enriched microbiota may promote host serotonin production, which is positively correlated with reproductive performance in our study, known to regulate follicle survival and oocyte maturation. CONCLUSION Our study provides a theoretical basis for understanding the interactions between gut microbes and the host. It highlights new insights into reassembling gut microbiota in sows with higher litter sizes and the role of serotonin-related microbiota and serotonin in fertility.
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Affiliation(s)
- Yanli Chen
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Yan Wang
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Weike Shaoyong
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Yanmin He
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Yalin Liu
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Siyu Wei
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Yujie Gan
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Lu Sun
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Youming Wang
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Xin Zong
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Yun Xiang
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Science Research, Jinhua, 321017, China
| | - Yizhen Wang
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China
| | - Mingliang Jin
- Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China.
- Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, 310058, China.
- Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, Hangzhou, 310058, China.
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Belelli D, Lambert JJ, Wan MLY, Monteiro AR, Nutt DJ, Swinny JD. From bugs to brain: unravelling the GABA signalling networks in the brain-gut-microbiome axis. Brain 2025; 148:1479-1506. [PMID: 39716883 PMCID: PMC12074267 DOI: 10.1093/brain/awae413] [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: 07/30/2024] [Revised: 11/21/2024] [Accepted: 12/01/2024] [Indexed: 12/25/2024] Open
Abstract
Convergent data across species paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function, mediating most neuronal inhibition. Until recently, GABA's role and specific molecular targets in the periphery within the BGM axis had received limited attention. Yet, GABA is produced by neuronal and non-neuronal elements of the BGM, and recently, GABA-modulating bacteria have been identified as key players in GABAergic gut systems, indicating that GABA-mediated signalling is likely to transcend physiological boundaries and species. We review the available evidence to better understand how GABA facilitates the integration of molecularly and functionally disparate systems to bring about overall homeostasis and how GABA perturbations within the BGM axis can give rise to multi-system medical disorders, thereby magnifying the disease burden and the challenges for patient care. Analysis of transcriptomic databases revealed significant overlaps between GABAAR subunits expressed in the human brain and gut. However, in the gut, there are notable expression profiles for a select number of subunits that have received limited attention to date but could be functionally relevant for BGM axis homeostasis. GABAergic signalling, via different receptor subtypes, directly regulates BGM homeostasis by modulating the excitability of neurons within brain centres responsible for gastrointestinal (GI) function in a sex-dependent manner, potentially revealing mechanisms underlying the greater prevalence of GI disturbances in females. Apart from such top-down regulation of the BGM axis, a diverse group of cell types, including enteric neurons, glia, enteroendocrine cells, immune cells and bacteria, integrate peripheral GABA signals to influence brain functions and potentially contribute to brain disorders. We propose several priorities for this field, including the exploitation of available technologies to functionally dissect components of these GABA pathways within the BGM, with a focus on GI and brain-behaviour-disease. Furthermore, in silico ligand-receptor docking analyses using relevant bacterial metabolomic datasets, coupled with advances in knowledge of GABAAR 3D structures, could uncover new ligands with novel therapeutic potential. Finally, targeted design of dietary interventions is imperative to advancing their therapeutic potential to support GABA homeostasis across the BGM axis.
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Affiliation(s)
- Delia Belelli
- GABA Labs (Research) Ltd., Hemel Hempstead HP2 5HD, UK
- Division of Neuroscience, School of Medicine, Medical Sciences Institute, Dundee University, Dundee DD1 5HL, UK
- School of Medicine, Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
| | - Jeremy J Lambert
- Division of Neuroscience, School of Medicine, Medical Sciences Institute, Dundee University, Dundee DD1 5HL, UK
| | - Murphy Lam Yim Wan
- School of Medicine, Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
| | - Ana Rita Monteiro
- School of Medicine, Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
| | - David J Nutt
- GABA Labs (Research) Ltd., Hemel Hempstead HP2 5HD, UK
- Division of Psychiatry, Department of Brain Sciences, Imperial College London, London W12 0NN, UK
| | - Jerome D Swinny
- School of Medicine, Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
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Liu T, Ma M, Wu Y, Asif IM, Chen D, Liu L, Zhang M, Chen Y, Li B, Wang L. Protective Effects of Fucoidan on Iodoacetamide-Induced Functional Dyspepsia via Modulation of 5-HT Metabolism and Microbiota. Int J Mol Sci 2025; 26:3273. [PMID: 40244137 PMCID: PMC11989908 DOI: 10.3390/ijms26073273] [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: 02/06/2025] [Revised: 02/26/2025] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
As the major polysaccharide in brown algae, fucoidan possesses broad biological abilities and has been reported to improve gastrointestinal health. Functional dyspepsia, a common non-organic disease, is a complex of symptoms mainly characterized by pathogenesis, such as visceral hypersensitivity, gastric dysmotility, and inflammation. To date, the effects of fucoidan in regulating functional dyspepsia with visceral sensitivity remains unclear. In the current study, iodoacetamide was employed to establish a mouse model of visceral hypersensitivity. Meanwhile, fucoidan was orally administrated for fourteen days. Indicators were conducted to evaluate the potential of fucoidan as the ingredient of complementary and alternative medicine for functional dyspepsia, such as levels of serum hormones, expression of receptors, and gut microbial profile. The results show that oral administration of fucoidan led to significant reductions in the secretion of 5-hydroxytryptamine, cortisol, and corticosterone. Additionally, it decreased the expression of 5-hydroxytryptamine-3 receptors, with regulation of 5-hydroxytryptamine metabolism and improvement of gut microbial imbalance. The above results suggest fucoidan could ameliorate visceral hypersensitivity by modulating 5-HT metabolism and microbiota. The current findings indicate that fucoidan has potential as a biological component in the adjuvant treatment of functional dyspepsia and for its expanded utilization in the food and medical fields.
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Affiliation(s)
- Tianxu Liu
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Muyuan Ma
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Yonglin Wu
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Ismail Muhammad Asif
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Daosen Chen
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Lichong Liu
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Minghui Zhang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Yijie Chen
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Bin Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
| | - Ling Wang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (T.L.); (M.M.)
- Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China
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Luo J, Xu Q, Xu S, Zhai L, Yuan CS, Bian Z. Decoding Abdominal Pain in Constipation-predominant Irritable Bowel Syndrome and Functional Constipation: Mechanisms and Managements. Curr Gastroenterol Rep 2025; 27:22. [PMID: 40095229 PMCID: PMC11914341 DOI: 10.1007/s11894-025-00967-7] [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] [Accepted: 02/12/2025] [Indexed: 03/19/2025]
Abstract
PURPOSE OF REVIEW Abdominal pain in constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) remains a difficult clinical challenge due to unclear pathophysiological mechanisms and limited pain-targeted treatments. This review critically evaluates the evidence on the underlying pain mechanisms in IBS-C and/or FC and explores management strategies, their limitations, and future directions. RECENT FINDINGS Most research on constipation-related pain is based on IBS-C patients or animal models, with limited studies focusing on FC. Visceral hypersensitivity, serotonin dysregulation, gut-brain axis dysfunction, and central/peripheral nervous system alterations are implicated in IBS-C pain, while FC pain is less studied and may be primarily linked to colonic distension and motility dysfunction. Management strategies include 5-HT4 agonists, GC-C agonists, chloride channel activators, psychological therapies, probiotics and complementary medicine. Despite available treatment options, managing abdominal pain in IBS-C and FC remains challenging due to heterogeneous pathophysiology and limited targeted therapies. While some interventions provide symptomatic relief, there is no universally effective treatment for abdominal pain across all patients. Future research should focus on identifying pain-specific biomarkers, refining diagnostic criteria, and integrating multi-omics data and neuroimaging techniques to better distinguish pain mechanisms in IBS-C versus FC and develop more precise, patient-centered interventions.
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Affiliation(s)
- Jingyuan Luo
- Vincent V.C. Woo Chinese Medicine Clinical Research Institute, School of Chinese Medicine, Hong Kong Baptist University, 3/F, Jockey Club School of Chinese Medicine Building, 7 Baptist University Road, Kowloon Tong, Hong Kong, SAR, China
- Center for Chinese Herbal Medicine Drug Development and School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China
| | - Qianqian Xu
- Vincent V.C. Woo Chinese Medicine Clinical Research Institute, School of Chinese Medicine, Hong Kong Baptist University, 3/F, Jockey Club School of Chinese Medicine Building, 7 Baptist University Road, Kowloon Tong, Hong Kong, SAR, China
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14214-8033, USA
| | - Shujun Xu
- Center for Chinese Herbal Medicine Drug Development and School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China
| | - Lixiang Zhai
- Center for Chinese Herbal Medicine Drug Development and School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China.
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research and Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4028, Chicago, IL, 60637, USA.
- Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, IL, 60637, USA.
| | - Zhaoxiang Bian
- Vincent V.C. Woo Chinese Medicine Clinical Research Institute, School of Chinese Medicine, Hong Kong Baptist University, 3/F, Jockey Club School of Chinese Medicine Building, 7 Baptist University Road, Kowloon Tong, Hong Kong, SAR, China.
- Center for Chinese Herbal Medicine Drug Development and School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China.
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Iliev ID, Ananthakrishnan AN, Guo CJ. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities. Nat Rev Microbiol 2025:10.1038/s41579-025-01163-0. [PMID: 40065181 DOI: 10.1038/s41579-025-01163-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/26/2025]
Abstract
Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.
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Affiliation(s)
- Iliyan D Iliev
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA.
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Jun Guo
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA
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Deljavan Ghodrati A, Comoglu T. Rifaximin and alternative agents in the management of irritable bowel syndrome: A comprehensive review. Arch Pharm (Weinheim) 2024; 357:e2400356. [PMID: 39041415 DOI: 10.1002/ardp.202400356] [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: 05/08/2024] [Revised: 06/29/2024] [Accepted: 07/01/2024] [Indexed: 07/24/2024]
Abstract
Rifaximin, a broad-spectrum antibiotic, boasts a unique chemical composition and pharmacokinetic profile, rendering it highly effective in treating irritable bowel syndrome (IBS). Its minimal systemic absorption confines its impact to the gastrointestinal (GI) tract, where it yields significant therapeutic benefits. This review examines rifaximin's physico-chemical attributes and its role in managing IBS symptoms. Its molecular structure facilitates intestinal lumen retention postoral administration, minimizing systemic exposure and adverse effects. This targeted action is crucial in addressing the gut microbiota's role in IBS pathophysiology. By modifying microbial populations and their metabolite production, rifaximin mitigates symptoms like bloating, irregular bowel habits, and abdominal pain associated with IBS. It achieves this by reducing pathogenic bacteria and altering bacterial metabolism, enhancing mucosal and immune function. Clinical trials affirm rifaximin's superiority over placebo and conventional therapies in alleviating overall IBS symptoms and addressing small intestine bacterial overgrowth (SIBO). Despite its promising efficacy and sustained symptom relief, further research is essential to optimize long-term effectiveness and dosing regimens. Rifaximin stands as a vital treatment option for IBS due to its distinctive properties and clinical utility; yet, ongoing investigation is imperative for maximizing its therapeutic benefits.
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Affiliation(s)
- Aylin Deljavan Ghodrati
- Department of Pharmaceutical Technology, Ankara University Faculty of Pharmacy, Ankara, Turkey
- Graduate School of Health Sciences, Ankara University, Ankara, Turkey
| | - Tansel Comoglu
- Department of Pharmaceutical Technology, Ankara University Faculty of Pharmacy, Ankara, Turkey
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Ranhotra HS. Discrete interplay of gut microbiota L-tryptophan metabolites in host biology and disease. Mol Cell Biochem 2024; 479:2273-2290. [PMID: 37861881 DOI: 10.1007/s11010-023-04867-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/24/2023] [Indexed: 10/21/2023]
Abstract
The gut microbiota and the host maintain a conjoint relationship and together achieve optimal physiology via a multitude of interactive signalling cues. Dietary-derived L-tryptophan (L-trp) is enzymatically metabolized by the resident symbiotic gut microbiota to indole and various indole derivatives. Indole and indole metabolites secreted by the gut bacteria act locally in the intestinal cells as well as distally and modulate tissue-specific functions which are beneficial to the host. Functions attributed to these microbial indole metabolites in the host include regulation of intestinal permeability, immunity and mucosal roles, inflammation, and insulin sensitivity. On the other hand, dysregulation of gut microbiota L-trp metabolism compromises the optimal availability of indole and indole metabolites and can induce the onset of metabolic disorders, inflammation, liver steatosis, and decrease gut barrier integrity. Gut dysbiosis is regarded as one of the prime reasons for this deregulated microbial-derived indole metabolites. A number of indole metabolites from the gut bacteria have been identified recently displaying variable affinity towards xenobiotic nuclear receptors. Microbial metabolite mimicry concept can be used to design and develop novel indole-moiety-containing compounds with higher affinity towards the receptors and efficacy in preclinical studies. Such compounds may serve as therapeutic drugs in clinical trials in the future. In this article, I review L-trp metabolism in the host and gut microbiota and the various physiological functions, patho-physiologies associated with the microbial-released indole metabolites in the host, including the metabolite mimicry-based concept to develop tailored indole-containing novel experimental drugs.
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Affiliation(s)
- Harmit S Ranhotra
- Department of Biochemistry, St. Edmund's College, Shillong, 793 003, India.
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8
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Khoo SC, Zhang N, Luang-In V, Goh MS, Sonne C, Ma NL. Exploring environmental exposomes and the gut-brain nexus: Unveiling the impact of pesticide exposure. ENVIRONMENTAL RESEARCH 2024; 250:118441. [PMID: 38350544 DOI: 10.1016/j.envres.2024.118441] [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: 07/17/2023] [Revised: 01/20/2024] [Accepted: 02/06/2024] [Indexed: 02/15/2024]
Abstract
This review delves into the escalating concern of environmental pollutants and their profound impact on human health in the context of the modern surge in global diseases. The utilisation of chemicals in food production, which results in residues in food, has emerged as a major concern nowadays. By exploring the intricate relationship between environmental pollutants and gut microbiota, the study reveals a dynamic bidirectional interplay, as modifying microbiota profile influences metabolic pathways and subsequent brain functions. This review will first provide an overview of potential exposomes and their effect to gut health. This paper is then emphasis the connection of gut brain function by analysing microbiome markers with neurotoxicity responses. We then take pesticide as example of exposome to elucidate their influence to biomarkers biosynthesis pathways and subsequent brain functions. The interconnection between neuroendocrine and neuromodulators elements and the gut-brain axis emerges as a pivotal factor in regulating mental health and brain development. Thus, manipulation of gut microbiota function at the onset of stress may offer a potential avenue for the prevention and treatment for mental disorder and other neurodegenerative illness.
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Affiliation(s)
- Shing Ching Khoo
- Biological Security and Sustainability (BioSES) Research Interest Group, Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia
| | - Nan Zhang
- Synerk Biotech, BioBay, Suzhou, 215000, China; Neuroscience Program, Department of Neurology, Houston Methodist Research Institute, TX, 77030, USA; Department of Neurology, Weill Cornell Medicine, New York, 10065, USA
| | - Vijitra Luang-In
- Natural Antioxidant Innovation Research Unit, Department of Biotechnology, Faculty of Technology, Mahasarakham University, Khamriang, Kantharawichai, Mahasarakham, 44150, Thailand
| | - Meng Shien Goh
- Biological Security and Sustainability (BioSES) Research Interest Group, Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia
| | - Christian Sonne
- Aarhus University, Faculty of Science and Technology, Department of Bioscience, Arctic Research Centre (ARC), Danish Centre for Environment and Energy (DCE), Frederiksborgvej 399, PO Box 358, DK-4000, Roskilde, Denmark
| | - Nyuk Ling Ma
- Biological Security and Sustainability (BioSES) Research Interest Group, Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia; Center for Global Health Research (CGHR), Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.
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Liang YF, Chen XQ, Zhang MT, Tang HY, Shen GM. Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders. Gut Liver 2024; 18:391-403. [PMID: 37551453 PMCID: PMC11096901 DOI: 10.5009/gnl220346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 04/26/2023] [Accepted: 05/22/2023] [Indexed: 08/09/2023] Open
Abstract
Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.
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Affiliation(s)
- Yi Feng Liang
- College of Acupuncture and Massage, Anhui University of Chinese Medicine, Hefei, China
| | - Xiao Qi Chen
- College of Acupuncture and Massage, Anhui University of Chinese Medicine, Hefei, China
| | - Meng Ting Zhang
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - He Yong Tang
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Guo Ming Shen
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
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10
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El-Salhy M, Gilja OH, Hatlebakk JG. Increasing the transplant dose and repeating faecal microbiota transplantation results in the responses of male patients with IBS reaching those of females. Scand J Gastroenterol 2024; 59:391-400. [PMID: 38084725 DOI: 10.1080/00365521.2023.2292479] [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: 11/03/2023] [Accepted: 12/04/2023] [Indexed: 04/04/2024]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) performed with a proper protocol is a safe treatment for IBS that has high efficacy and durable effects. Females have been reported to respond better than males to FMT. The present study aimed at determining whether increasing the transplant dose or repeating FMT improve the responses of males to FMT. METHODS This study included 186 IBS patients (131 females and 55 males) who were randomized at a 1:1:1 ratio to receive 90 g of donor faeces once into the large intestine, once into the small intestine or twice into the small intestine. Patients completed five questionnaires that assessed their symptoms and quality of life, and provided faecal samples at baseline and at 3, 6 and 12 months after FMT. The faecal bacterial profile and dysbiosis index were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. RESULTS The response rates to FMT at all observation times did not differ significantly between females and males regardless of the transplant administration route or whether it was repeated. Faecal Alistipes levels were higher in females than in males at baseline and increased in both females and males after FMT. In the repeated group, the Alistipes levels did not differ between females and males after FMT. CONCLUSIONS Increasing the transplant dose and repeating FMT results in the responses of male IBS patients to FMT reaching those of females regardless of the administration route. Alistipes spp. levels appear to play a role in this improvement.www.clinicaltrials.gov (NCT04236843).
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Stord Hospital, Stord, Norway
- Department of Clinical Medicine and Department of Gastroenterology, University of Bergen, Bergen, Norway
| | - Odd Helge Gilja
- Department of Clinical Medicine and Department of Gastroenterology, University of Bergen, Bergen, Norway
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Department of Clinical Medicine and Department of Gastroenterology, University of Bergen, Bergen, Norway
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11
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Chojnacki J, Konrad P, Mędrek-Socha M, Kaczka A, Błońska A, Zajdel R, Chojnacki C, Gąsiorowska A. The Variability of Tryptophan Metabolism in Patients with Mixed Type of Irritable Bowel Syndrome. Int J Mol Sci 2024; 25:2550. [PMID: 38473797 DOI: 10.3390/ijms25052550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 02/12/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms.
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Affiliation(s)
- Jan Chojnacki
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Paulina Konrad
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Marta Mędrek-Socha
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Aleksandra Kaczka
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Aleksandra Błońska
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Radosław Zajdel
- Department of Computer Science in Economics, University of Lodz, 90-255 Lodz, Poland
| | - Cezary Chojnacki
- Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland
| | - Anita Gąsiorowska
- Department of Gastroenterology, Medical University of Lodz, 92-213 Lodz, Poland
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12
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Akram N, Faisal Z, Irfan R, Shah YA, Batool SA, Zahid T, Zulfiqar A, Fatima A, Jahan Q, Tariq H, Saeed F, Ahmed A, Asghar A, Ateeq H, Afzaal M, Khan MR. Exploring the serotonin-probiotics-gut health axis: A review of current evidence and potential mechanisms. Food Sci Nutr 2024; 12:694-706. [PMID: 38370053 PMCID: PMC10867509 DOI: 10.1002/fsn3.3826] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 10/24/2023] [Accepted: 11/01/2023] [Indexed: 02/20/2024] Open
Abstract
Modulatory effects of serotonin (5-Hydroxytryptamine [5-HT]) have been seen in hepatic, neurological/psychiatric, and gastrointestinal (GI) disorders. Probiotics are live microorganisms that confer health benefits to their host. Recent research has suggested that probiotics can promote serotonin signaling, a crucial pathway in the regulation of mood, cognition, and other physiological processes. Reviewing the literature, we find that peripheral serotonin increases nutrient uptake and storage, regulates the composition of the gut microbiota, and is involved in mediating neuronal disorders. This review explores the mechanisms underlying the probiotic-mediated increase in serotonin signaling, highlighting the role of gut microbiota in the regulation of serotonin production and the modulation of neurotransmitter receptors. Additionally, this review discusses the potential clinical implications of probiotics as a therapeutic strategy for disorders associated with altered serotonin signaling, such as GI and neurological disorders. Overall, this review demonstrates the potential of probiotics as a promising avenue for the treatment of serotonin-related disorders and signaling of serotonin.
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Affiliation(s)
- Noor Akram
- Department of Food and NutritionGovernment College University FaisalabadFaisalabadPakistan
| | - Zargham Faisal
- Department of Human NutritionBahauddin Zakariya University MultanMultanPakistan
| | - Rushba Irfan
- Faculty of Food Nutrition & Home SciencesUniversity of AgricultureFaisalabadPakistan
| | - Yasir Abbas Shah
- Natural & Medical Science Research CenterUniversity of NizwaNizwaOman
| | - Syeda Ayesha Batool
- Department of Food ScienceGovernment College University FaisalabadFaisalabadPakistan
| | - Toobaa Zahid
- Department of Food and NutritionGovernment College University FaisalabadFaisalabadPakistan
| | - Aqsa Zulfiqar
- Department of Food and NutritionGovernment College University FaisalabadFaisalabadPakistan
| | - Areeja Fatima
- National Institute of Food Science & TechnologyUniversity of AgricultureFaisalabadPakistan
| | - Qudsia Jahan
- Department of Food and NutritionGovernment College University FaisalabadFaisalabadPakistan
| | - Hira Tariq
- Department of Food and NutritionGovernment College University FaisalabadFaisalabadPakistan
| | - Farhan Saeed
- Department of Food ScienceGovernment College University FaisalabadFaisalabadPakistan
| | - Aftab Ahmed
- Department of Nutritional SciencesGovernment College University FaisalabadFaisalabadPakistan
| | - Aasma Asghar
- Department of Nutritional SciencesGovernment College University FaisalabadFaisalabadPakistan
| | - Huda Ateeq
- Department of Food ScienceGovernment College University FaisalabadFaisalabadPakistan
| | - Muhammad Afzaal
- Department of Food ScienceGovernment College University FaisalabadFaisalabadPakistan
| | - Mahbubur Rahman Khan
- Department of Food Processing and PreservationHajee Mohammad Danesh Science & Technology UniversityDinajpurBangladesh
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13
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Wal A, Wal P, Verma N, Pandey SS, Krishnan K, Bhowmick M. Children and Adolescents with Irritable Bowel Syndrome: Treatment and Management. Curr Pediatr Rev 2024; 20:166-177. [PMID: 36443973 DOI: 10.2174/1573396319666221128094843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/13/2022] [Accepted: 09/02/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a disorder that causes stomach pain in children and adolescents. It may also impact one's quality of life. IBS is linked to gastrointestinal issues such as diarrhoea and constipation. Despite the identification of several potential pathophysiological pathways, the aetiology of IBS remained unknown. OBJECTIVE The aim of this paper is to discuss the diagnosis, pathogenesis, case studies and treatment of Irritable bowel syndrome in children and adolescents. METHODS This systematic review covered relevant papers from the previous ten years that were accessible in Science Direct, Elsevier, NCBI, and Web of Science related to the pathophysiology and function of pharmacological drugs such as antidepressants, antispasmodics, prokinetics, and antibiotics in children with irritable bowel syndrome. RESULTS Only a few prospective therapy techniques have been investigated in children, and even fewer of those have been demonstrated to be effective. This article presents case studies including 50-59 children, which demonstrate a favourable acceptable impact that is more effective than a placebo in terms of reducing symptoms and improving the overall quality of life in children who have irritable bowel syndrome. Furthermore, the majority of the pathophysiological explanations and treatment options discussed are based on adult studies. These major issues arose when treating paediatric IBS, and they must be addressed in order to properly treat children with IBS. Trials that focus on many combinations of pharmacological and non-pharmacological therapies seem to be more helpful. DISCUSSION In recent years, a number of systematic reviews have been conducted to evaluate the efficacy of medication treatments in children for IBS; however, the dependability of these systematic reviews needs to be further investigated owing to the various experimental designs and levels of evidence used. This article highlights paediatric therapy options, including pharmaceutical medications such as antidepressants, antispasmodics, prokinetics, and antibiotics. The goal is to alleviate IBS symptoms while also enhancing the quality of life for children with this illness.
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Affiliation(s)
- Ankita Wal
- Department of Pharmacy, Pranveer Singh Institute of Technology, Nh2 Kanpur Agra Highway Bhaunti, Kanpur, UP, India
| | - Pranay Wal
- Department of Pharmacy, Pranveer Singh Institute of Technology, Nh2 Kanpur Agra Highway Bhaunti, Kanpur, UP, India
| | - Neha Verma
- Department of Pharmacy, Pranveer Singh Institute of Technology, Nh2 Kanpur Agra Highway Bhaunti, Kanpur, UP, India
| | | | - Karthickeyan Krishnan
- Institute of Science Technology & Advanced Studies Pallavaram, Chennai, 600117, Tamil Nadu, 600117, India
| | - Mithun Bhowmick
- D101 Shikshak Niketan, Campus of Bengal College of Pharmaceutical Sciences and Research, Bidhananagar Durgapur, West Bengal, 713212, India
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14
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Dothel G, Barbaro MR, Di Vito A, Ravegnini G, Gorini F, Monesmith S, Coschina E, Benuzzi E, Fuschi D, Palombo M, Bonomini F, Morroni F, Hrelia P, Barbara G, Angelini S. New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics. J Gastroenterol 2023; 58:605-621. [PMID: 37160449 PMCID: PMC10307698 DOI: 10.1007/s00535-023-01997-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 04/19/2023] [Indexed: 05/11/2023]
Abstract
Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut-brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators of several mechanisms involved in IBS pathophysiology. These epigenetic factors include biomolecular mechanisms inducing chromosome-related and heritable changes in gene expression regardless of DNA coding sequence. Accordingly, altered gut microbiota may increase the production of metabolites such as sodium butyrate, a prominent inhibitor of histone deacetylases. Patients with IBS showed an increased amount of butyrate-producing microbial phila as well as an altered profile of methylated genes and micro-RNAs (miRNAs). Importantly, gene acetylation as well as specific miRNA profiles are involved in different IBS mechanisms and may be applied for future diagnostic purposes, especially to detect increased gut permeability and visceromotor dysfunctions. In this review, we summarize current knowledge of the role of epigenetics in IBS pathophysiology.
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Affiliation(s)
- Giovanni Dothel
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- Connect By Circular Lab SRL, Madrid, Spain
| | | | - Aldo Di Vito
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Gloria Ravegnini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Francesca Gorini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Sarah Monesmith
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Emma Coschina
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Eva Benuzzi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Daniele Fuschi
- IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Marta Palombo
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesca Bonomini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabiana Morroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Patrizia Hrelia
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sabrina Angelini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- Inter-Departmental Center for Health Sciences & Technologies, CIRI-SDV, University of Bologna, Bologna, Italy
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15
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Yang H, Wu C, Chen L, Chang X, Luo G, Wu K, Tian W. A. macrocephala polysaccharide induces alterations to gut microbiome and serum metabolome in constipated mice. Microb Pathog 2023; 178:106084. [PMID: 36990166 DOI: 10.1016/j.micpath.2023.106084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/19/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023]
Abstract
Atractylodes macrocephala polysaccharide (AC1) is extracted from the root of the Chinese herb Atractylodes Macrocephala and is used in the treatment of constipation due to its effects on strengthening cellular immunity and regulating intestinal function. In this study, Metagenomics and Metabolomic are used to analyze the effects of AC1 on the gut microbiota and host metabolites in mice models of constipation. The results show that the abundance of Lachnospiraceae_bacterium_A4, Bact-oides_vulgatus and Prevotella_sp_CAG:891 increased significantly, indicating that AC1-targeted strain modulation effectively alleviated the dysbiosis of the gut microbiota. Besides, the microbial alterations also influenced the metabolic pathways of the mice, including tryptophan metabolism, unsaturated fatty acid synthesis and bile acid metabolism. The physiological parameters of the mice treated with AC1 are improved, such as tryptophan in the colon, 5-hydroxytryptamine (5-HT) and short-chain fatty acids (SCFAs). In conclusion, AC1 as a probiotic can regulate intestinal flora to normal levels and achieve the effect of treating constipation.
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16
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The role of hippocampal 5-HT 1D and 5-HT 1F receptors on learning and memory in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023:10.1007/s00210-023-02411-x. [PMID: 36749399 DOI: 10.1007/s00210-023-02411-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 01/27/2023] [Indexed: 02/08/2023]
Abstract
Serotonin is a neurotransmitter, which is involved in memory via its receptors. The 5-HT1D and 5-HT1F receptors mainly exist in the hippocampus, which plays an important role in memory processing. However, few studies have assessed the effect of these serotonin receptors on memory. We evaluated the effect of a 5-HT1D receptor agonist, PNU142633, 5-HT1D receptor antagonist, BRL15572 hydrochloride, and 5-HT1F receptor agonist, LY344864, on the recognition and avoidance memory in the hippocampus area. Fifty adult male Wistar rats weighing 200-250 g were divided into the control, sham-operated, PNU, BRL, and LY groups (n=10 per group). Bilateral guide cannulas were implanted into the dentate gyrus area of the hippocampus. The drugs were administered at the dose of 1 μg/μl before the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The results showed that in the NOR test, the administration of PNU and LY had no significant effect on recognition index; however, the recognition index was increased by BRL. In the PAL test, the administration of PNU had no significant effect on recognition index, but the administration of BRL and LY increased the time spent in the dark compartment of the apparatus and decreased the step-through latency into the dark compartment apparatus. It can be concluded that the inhibition of the hippocampal 5-HT1D receptor improved cognition memory but impaired avoidance memory. Activation of the hippocampal 5-HT1F receptor had no effect on cognitive memory but impaired avoidance memory.
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17
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Zhai L, Huang C, Ning Z, Zhang Y, Zhuang M, Yang W, Wang X, Wang J, Zhang L, Xiao H, Zhao L, Asthana P, Lam YY, Chow CFW, Huang JD, Yuan S, Chan KM, Yuan CS, Lau JYN, Wong HLX, Bian ZX. Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. Cell Host Microbe 2023; 31:33-44.e5. [PMID: 36495868 DOI: 10.1016/j.chom.2022.11.006] [Citation(s) in RCA: 81] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 09/06/2022] [Accepted: 11/15/2022] [Indexed: 12/14/2022]
Abstract
Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.
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Affiliation(s)
- Lixiang Zhai
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China
| | - Chunhua Huang
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Ziwan Ning
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Yijing Zhang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Min Zhuang
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China
| | - Wei Yang
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China
| | - Xiaolei Wang
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Jingjing Wang
- Department of Computer Science, Hong Kong Baptist University, Hong Kong SAR, China
| | - Lu Zhang
- Department of Computer Science, Hong Kong Baptist University, Hong Kong SAR, China
| | - Haitao Xiao
- School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China
| | - Ling Zhao
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Pallavi Asthana
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Yan Y Lam
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China
| | - Chi Fung Willis Chow
- Center for Systems Biology Dresden, Max Planck Institute for Molecular Cell and Biology, Dresden, Germany
| | - Jian-Dong Huang
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Shuofeng Yuan
- State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Kui Ming Chan
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, USA
| | - Johnson Yiu-Nam Lau
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | | | - Zhao-Xiang Bian
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
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18
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Song Y, Yin D, Zhang Z, Chi L. Research progress of treatment of functional dyspepsia with traditional Chinese medicine compound based on cell signal pathway. Front Pharmacol 2023; 13:1089231. [PMID: 36699059 PMCID: PMC9868459 DOI: 10.3389/fphar.2022.1089231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/15/2022] [Indexed: 01/11/2023] Open
Abstract
Functional dyspepsia (FD) is the most common clinical gastrointestinal disease, with complex and prolonged clinical symptoms. The prevalence of FD is increasing year by year, seriously affecting the quality of life of patients. The main causes of FD are related to abnormal gastrointestinal dynamics, increased visceral sensitivity, Helicobacter pylori (HP) infection, intestinal flora disturbance and psychological factors. A review of the relevant literature reveals that the mechanisms of traditional Chinese medicine (TCM) in the treatment of FD mainly involve the following pathways:5-HT signal pathway, AMPK signal pathway,C-kit signal pathway, CRF signal pathway, PERK signal pathway,NF-κB signal pathway. Based on a holistic concept, TCM promotes gastrointestinal motility, regulates visceral sensitivity and alleviates gastrointestinal inflammation through multiple signal pathways, reflecting the advantages of multi-level, multi-pathway and multi-targeted treatment of FD.
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Affiliation(s)
- Yujiao Song
- Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China,*Correspondence: Yujiao Song, ; Defei Yin, ; Zhenyi Zhang, ; Lili Chi,
| | - Defei Yin
- Digestive System Department II, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China,*Correspondence: Yujiao Song, ; Defei Yin, ; Zhenyi Zhang, ; Lili Chi,
| | - Zhenyi Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China,*Correspondence: Yujiao Song, ; Defei Yin, ; Zhenyi Zhang, ; Lili Chi,
| | - Lili Chi
- Digestive System Department II, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China,*Correspondence: Yujiao Song, ; Defei Yin, ; Zhenyi Zhang, ; Lili Chi,
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19
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Intestinal Flora Affect Alzheimer's Disease by Regulating Endogenous Hormones. Neurochem Res 2022; 47:3565-3582. [DOI: 10.1007/s11064-022-03784-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/13/2022] [Accepted: 10/01/2022] [Indexed: 11/25/2022]
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20
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Meng YY, Wang EK, Wang YS, Feng Y, Hang L, Yuan JY. Progress in traditional Chinese medicine study of constipation predominant irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2022; 30:892-896. [DOI: 10.11569/wcjd.v30.i20.892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The etiology and pathogenesis of constipation predominant irritable bowel syndrome (IBS-C) have not been fully elucidated. The lack of satisfactory treatment and the rising incidence of IBS-C often affect the lives of patients in different degrees. This paper summarizes the understanding of the etiology, pathogenesis, and common effective treatment methods for IBS-C in recent years from the perspective of traditional Chinese medicine (TCM), with an aim to provide a reference for further study of the role of TCM in IBS-C treatment.
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Affiliation(s)
- Yang-Yang Meng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China,Yueyang Hospital of Integrated Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - En-Kang Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yin-Shu Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Ya Feng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Lu Hang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jian-Ye Yuan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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21
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Romano L, Granata L, Fusco F, Napolitano L, Cerbone R, Priadko K, Sciorio C, Mirone V, Romano M. Sexual Dysfunction in Patients With Chronic Gastrointestinal and Liver Diseases: A neglected Issue. Sex Med Rev 2022; 10:620-631. [PMID: 34353738 DOI: 10.1016/j.sxmr.2021.02.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/20/2021] [Accepted: 02/25/2021] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Normal sexual activity is an important determinant of quality of life. Unfortunately, several chronic health disorders are associated with an impaired sexual function. OBJECTIVE To provide coverage of the current literature on prevalence and pathophysiology of sexual dysfunction in patients with gastrointestinal and liver disorders METHODS: A Comprehensive review of the literature on the prevalence of sexual dysfunction in chronic gastrointestinal and liver disorders, assessing the underlying mechanism (s) was performed. RESULTS Many gastrointestinal disorders, either functional or organic, are associated with some degree of sexual dysfunction. The main pathogenic mechanisms are: (i) the disease itself causing fatigue, anxiety or depression with a potential alteration of self-esteem; (ii) worry of transmitting a potential infectious agent through sexual activity; (iii) alteration of the endocrine mechanisms which are necessary for normal sexual functioning; (iv) chronic pro- inflammatory conditions which may cause endothelial dysfunction and abnormal vascular responses; (v) iatrogenic. CONCLUSION Based on this review, a thorough evaluation of sexual function through validated questionnaires and/or psychological interviews with patients with chronic gastrointestinal disorders should be part of the clinical assessment in order to timely diagnose and possibly treat sexual dysfunction in this clinical setting. L Romano, L Granata, F Fusco, et al. Sexual Dysfunction in Patients With Chronic Gastrointestinal and Liver Diseases: A neglected Issue. Sex Med Rev 2022;10:620-631.
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Affiliation(s)
- Lorenzo Romano
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy
| | - Lucia Granata
- Dipartimento di Medicina di Precisione, Hepato-Gastroenterology Unit, Università della Campania Luigi Vanvitelli, Napoli, Italy
| | - Ferdinando Fusco
- Department of Woman, Child and General and Specialized Surgery, Urology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Luigi Napolitano
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy
| | - Rosa Cerbone
- Dipartimento di Medicina di Precisione, Hepato-Gastroenterology Unit, Università della Campania Luigi Vanvitelli, Napoli, Italy
| | - Kateryna Priadko
- Dipartimento di Medicina di Precisione, Hepato-Gastroenterology Unit, Università della Campania Luigi Vanvitelli, Napoli, Italy
| | | | - Vincenzo Mirone
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy
| | - Marco Romano
- Dipartimento di Medicina di Precisione, Hepato-Gastroenterology Unit, Università della Campania Luigi Vanvitelli, Napoli, Italy
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22
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Chen Z, Feng J, Hu S, Hua Y, Ma S, Fu W, Yang Q, Zhang X. Bacillus Subtilis Promotes the Release of 5-HT to Regulate Intestinal Peristalsis in STC Mice via Bile Acid and Its Receptor TGR5 Pathway. Dig Dis Sci 2022; 67:4410-4421. [PMID: 34797444 DOI: 10.1007/s10620-021-07308-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 10/26/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Slow transit constipation (STC) is caused by intestinal peristalsis dysfunction and is closely associated with disturbance of the intestinal microecological balance. Bacillus subtilis plays a positive role in the treatment of STC, but its mechanism needs to be further explored. AIMS The purpose of the present study was to explore the effects and mechanism of B. subtilis on the pathophysiology of STC. METHODS A STC mouse model was established with compound diphenoxylate, following which B. subtilis was used to treat STC. The effects and possible mechanism of B. subtilis on STC were investigated by assessing intestinal motility, histology of the colon, release of 5-HT in enterochromaffin cells (ECs) and the TGR5/TRPA1 pathway. Moreover, LC-MS targeted metabolomics was used to analyze the regulation of Bacillus subtilis on bile acid metabolisms in STC mice. RESULTS Bacillus subtilis significantly increased 24 h defecations, fecal moisture and intestinal transport rate of STC mice, improved pathological damage of the colon and showed protective effects on the intestinal tract. The release of 5-HT from ECs and the bile acid receptor TGR5/TRPA1 pathway were significantly increased in STC mice treated with B. subtilis. In addition, the metabolomics results showed that the bile acid contents of STC mice were significantly decreased, and B. subtilis could increase the bile acid composition and content of STC mice. CONCLUSION Bacillus subtilis regulates intestinal peristalsis of STC by promoting the release of 5-HT from ECs through bile acid metabolism and its receptor TGR5 pathway and plays a positive role in the treatment of STC.
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Affiliation(s)
- Zhenhai Chen
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Jiangyi Feng
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Song Hu
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Ye Hua
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Shaying Ma
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Weijie Fu
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Qian Yang
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China
| | - Xin Zhang
- Department of General Surgery, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing, 400014, China.
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23
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LMWP (S3-3) from the Larvae of Musca domestica Alleviate D-IBS by Adjusting the Gut Microbiota. Molecules 2022; 27:molecules27144517. [PMID: 35889391 PMCID: PMC9324334 DOI: 10.3390/molecules27144517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 07/03/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
Diarrhea-based Irritable Bowel Syndrome (D-IBS) and diarrhea are both associated with ecological imbalance of the gut microbiota. Low Molecular Weight Peptides (LMWP) from the larvae of Musca domestica have been shown to be effective in the treatment of diarrhea and regulation of gut microbiota. Meanwhile, the single polypeptide S3-3 was successfully isolated and identified from LMWP in our previous studies. It remains unclear exactly whether and how LMWP (S3-3) alleviate D-IBS through regulating gut microbiota. We evaluated the gut microbiota and pharmacology to determine the regulation of gut microbiota structure and the alleviating effect on D-IBS through LMWP (S3-3). The rates of loose stools, abdominal withdrawal reflex (AWR) and intestinal tract motility results revealed that LMWP (S3-3) from the larvae of Musca domestica had a regulating effect against diarrhea, visceral hypersensitivity and gastrointestinal (GI) dysfunction in D-IBS model mice. Additionally, 16S rRNA gene sequencing was utilized to examine the gut microbiota, which suggests that LMWP induce structural changes in the gut microbiota and alter the levels of the following gut microbiota: Bacteroidetes, Proteobacteria and Verrucomicrobia. LMWP putatively functioned through regulating 5-HT, SERT, 5-HT2AR, 5-HT3AR and 5-HT4R according to the results of ELISA, qRT-PCR and IHC. The findings of this study will contribute to further understanding how LMWP (S3-3) attenuate the effects of D-IBS on diarrhea, visceral hypersensitivity and GI dysfunction.
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24
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Lacy BE, Brenner DM, Chey WD. Re-evaluation of the Cardiovascular Safety Profile of Tegaserod: A Review of the Clinical Data. Clin Gastroenterol Hepatol 2022; 20:e682-e695. [PMID: 34048937 DOI: 10.1016/j.cgh.2021.05.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/23/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Tegaserod is a 5-HT4 receptor agonist approved for irritable bowel syndrome with constipation in women <65 years of age without a history of cardiovascular ischemic events. Safety data are presented from 2 external adjudications from the 2018 Gastrointestinal Drugs Advisory Committee meeting supporting tegaserod's reintroduction after its voluntary 2007 withdrawal. Withdrawal was based on an internal adjudication using pooled placebo-controlled tegaserod data to identify potential cardiovascular ischemic signals. METHODS An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (tegaserod: n = 20; placebo: n = 4) identified internally. A second independent external adjudication further evaluated these events. RESULTS A total of 18,645 patients were included (tegaserod: n = 11,614; placebo: n = 7031). The first adjudication identified 14 (0.075%) events (tegaserod: n = 13 [0.11%]; placebo: n = 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52-34.74; P = .273). All tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women <65 years of age without a history of cardiovascular ischemic events and ≤1 cardiovascular risk factor receiving tegaserod experienced no major adverse cardiovascular event(s). CONCLUSIONS Two independent, external adjudications suggest that tegaserod is safe for women <65 years of age with irritable bowel syndrome with constipation, no history of cardiovascular ischemic events, and ≤1 cardiovascular risk factor.
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Affiliation(s)
- Brian E Lacy
- Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
| | - Darren M Brenner
- Department of Medicine (Gastroenterology and Hepatology), Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - William D Chey
- Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, Michigan
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25
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Almeida PP, Valdetaro L, Thomasi BBDM, Stockler-Pinto MB, Tavares-Gomes AL. High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility. Obes Rev 2022; 23:e13404. [PMID: 34873814 DOI: 10.1111/obr.13404] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/25/2021] [Accepted: 11/15/2021] [Indexed: 01/09/2023]
Abstract
Obesity is a chronic disease that affects various physiological systems. Among them, the gastrointestinal tract appears to be a main target of this disease. High-fat diet (HFD) animal models can help recapitulate the classic signs of obesity and present a series of gastrointestinal alterations, mainly dysmotility. Because intestinal motility is governed by the enteric nervous system (ENS), enteric neurons, and glial cells have been studied in HFD models. Given the importance of the ENS in general gut physiology, this review aims to discuss the relationship between HFD-induced neuroplasticity and gut dysmotility observed in experimental models. Furthermore, we highlight components of the gut environment that might influence enteric neuroplasticity, including gut microbiota, enteric glio-epithelial unit, serotonin release, immune cells, and disturbances such as inflammation and oxidative stress.
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Affiliation(s)
| | - Luisa Valdetaro
- Postgraduate Program in Neurosciences, Fluminense Federal University, Niterói, Brazil
| | | | - Milena Barcza Stockler-Pinto
- Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University, Niterói, Brazil.,Postgraduate Program in Nutrition Sciences, Fluminense Federal University, Niterói, Brazil
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26
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Gamal NG, Abd El-Salam RM, Gadelrub LN, Ahmed-Farid OA, Khayyal MT. The herbal preparation STW 5 affects serotonergic pathways in the brain and colon as well as stress parameters in experimental irritable bowel syndrome. Neurogastroenterol Motil 2022; 34:e14301. [PMID: 34817922 DOI: 10.1111/nmo.14301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/10/2021] [Accepted: 11/10/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Exposure to stress has been related to disturbance in 5-hydroxytryptamine (5-HT) signaling in the brain-gut axis and is considered as a major predisposing factor for the development of irritable bowel syndrome (IBS). The present study aimed to investigate the possible involvement of 5-HT and some other stress-related parameters in the effectiveness of STW 5 against stress-induced IBS. METHODS Rats were subjected to restraint stress (RS) for 1 h/day for 14 consecutive days to induce IBS-like symptoms and were given STW 5 orally at the same time. At the end of the experiment, blood samples were withdrawn, then animals were euthanized and the brain hippocampi, cerebral cortices, as well as colons were isolated for biochemical and histopathological assessments. RESULTS RS increased the plasma corticotrophin releasing factor (CRF) with concomitant increase in hippocampal and cortical 5-HT levels, as well as mast cell inflammatory mediators, oxidative stress biomarkers, and histopathological inflammatory changes observed in rat colon. It also decreased the colonic content of 5-HT with consequent decrease in fecal pellet output (FPO). Treatment with STW 5 protected against these changes. CONCLUSION The protective effect of STW 5 against RS-induced IBS is related to its ability to normalize the induced changes in 5-HT in the brain-gut axis and counteract the stress-induced oxidative stress and inflammation.
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Affiliation(s)
- Nehal G Gamal
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Rania M Abd El-Salam
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | | | - Omar A Ahmed-Farid
- Physiology Department, National Organization for Drug Control and Research, Cairo, Egypt
| | - Mohamed T Khayyal
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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27
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Banskota S, Khan WI. Gut-derived serotonin and its emerging roles in immune function, inflammation, metabolism and the gut-brain axis. Curr Opin Endocrinol Diabetes Obes 2022; 29:177-182. [PMID: 35197425 DOI: 10.1097/med.0000000000000713] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW To shed light on the recently uncovered diverse role of serotonin (5-hydroxytryptamine; 5-HT) in the regulation of immune functions, inflammation, metabolism, and gut-brain axis. RECENT FINDINGS Peripheral 5-HT which accounts for approximately 95% of the total is largely synthesized in the gut by enterochromaffin cells. Enterochromaffin cells release 5-HT in response to various stimuli including microbial products. Released 5-HT influences secretomotor, sensory and immune functions as well as inflammatory processes in the gut. 5-HT released from enterochromaffin cells enters circulation and is taken up and concentrated in platelets. 5-HT released from the activated platelets interacts with different organs to alter their metabolic activity. 5-HT also serves as a link in the gut-brain axis. SUMMARY Emerging evidence regarding the role of peripheral 5-HT in the regulation of various physiological and pathophysiological conditions opens up new targets for researchers to explore and for clinicians to treat and manage different diseases associated with the altered 5-HT signalling.
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Affiliation(s)
- Suhrid Banskota
- Department of Pathology and Molecular Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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28
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Rezzani R, Franco C, Franceschetti L, Gianò M, Favero G. A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role. Int J Mol Sci 2022; 23:ijms23073758. [PMID: 35409109 PMCID: PMC8998884 DOI: 10.3390/ijms23073758] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/25/2022] [Accepted: 03/28/2022] [Indexed: 12/11/2022] Open
Abstract
The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic-nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.
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Affiliation(s)
- Rita Rezzani
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; (C.F.); (L.F.); (M.G.); (G.F.)
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs—(ARTO)”, University of Brescia, 25123 Brescia, Italy
- Italian Society of Orofacial Pain (SISDO), 25123 Brescia, Italy
- Correspondence: ; Tel.: +39-0303-717-483
| | - Caterina Franco
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; (C.F.); (L.F.); (M.G.); (G.F.)
| | - Lorenzo Franceschetti
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; (C.F.); (L.F.); (M.G.); (G.F.)
| | - Marzia Gianò
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; (C.F.); (L.F.); (M.G.); (G.F.)
| | - Gaia Favero
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; (C.F.); (L.F.); (M.G.); (G.F.)
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs—(ARTO)”, University of Brescia, 25123 Brescia, Italy
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29
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Orlando A, Chimienti G, Notarnicola M, Russo F. The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems. Int J Mol Sci 2022; 23:ijms23031098. [PMID: 35163022 PMCID: PMC8835524 DOI: 10.3390/ijms23031098] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/10/2022] [Accepted: 01/17/2022] [Indexed: 02/05/2023] Open
Abstract
Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.
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Affiliation(s)
- Antonella Orlando
- Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy;
| | - Guglielmina Chimienti
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy;
| | - Maria Notarnicola
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy;
| | - Francesco Russo
- Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy;
- Correspondence: ; Tel.: +39-080-4994315
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30
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Jannini TB, Lorenzo GD, Bianciardi E, Niolu C, Toscano M, Ciocca G, Jannini EA, Siracusano A. Off-label Uses of Selective Serotonin Reuptake Inhibitors (SSRIs). Curr Neuropharmacol 2022; 20:693-712. [PMID: 33998993 PMCID: PMC9878961 DOI: 10.2174/1570159x19666210517150418] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/22/2021] [Accepted: 05/05/2021] [Indexed: 11/22/2022] Open
Abstract
Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are highly versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. Thus, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than a serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by nonpsychiatrists. Thus, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.
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Affiliation(s)
- Tommaso B. Jannini
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Giorgio D. Lorenzo
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- IRCCS-Fondazione Santa Lucia, Rome, Italy
| | | | - Cinzia Niolu
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Massimiliano Toscano
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
- Department of Neurology, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
| | - Giacomo Ciocca
- Department of Dynamic and Clinical Psychology, and Health Studies, Sapienza University of Rome, Rome, Italy
| | | | - Alberto Siracusano
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
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Chen M, Ruan G, Chen L, Ying S, Li G, Xu F, Xiao Z, Tian Y, Lv L, Ping Y, Cheng Y, Wei Y. Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front Endocrinol (Lausanne) 2022; 13:817100. [PMID: 35250873 PMCID: PMC8888441 DOI: 10.3389/fendo.2022.817100] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 01/05/2022] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology. IBS is caused by a disruption in the gut-brain axis. Given the importance of the gut microbiota in maintaining local and systemic homeostasis of immunity, endocrine, and other physiological processes, the microbiota-gut-brain axis has been proposed as a key regulator in IBS. Neurotransmitters have been shown to affect blood flow regulation, intestinal motility, nutrient absorption, the gastrointestinal immune system, and the microbiota in recent studies. It has the potential role to play a function in the pathophysiology of the gastrointestinal and neurological systems. Transmitters and their receptors, including 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and histamine, play an important role in IBS, especially in visceral sensitivity and gastrointestinal motility. Studies in this field have shed light on revealing the mechanism by which neurotransmitters act in the pathogenesis of IBS and discovering new therapeutic strategies based on traditional pharmacological approaches that target the nervous system or novel therapies that target the microbiota.
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Affiliation(s)
- Minjia Chen
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Pathogenic Biology and Immunology, School of Basic Medicine, Ningxia Medical University, Yinchuan, China
| | - Guangcong Ruan
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lu Chen
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Senhong Ying
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guanhu Li
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Fenghua Xu
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhifeng Xiao
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yuting Tian
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Linling Lv
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Ping
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi Cheng
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Yi Cheng,
| | - Yanling Wei
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Yanling Wei, ; Yi Cheng,
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Fecal Microbiota Signatures Are Not Consistently Related to Symptom Severity in Irritable Bowel Syndrome. Dig Dis Sci 2022; 67:5137-5148. [PMID: 35624331 PMCID: PMC9587953 DOI: 10.1007/s10620-022-07543-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 03/01/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent functional bowel disorder, but its pathophysiology is still unknown. Although a microbial signature associated with IBS severity has been suggested, its association with IBS severity still remains largely unknown. AIMS This study aims to assess longitudinal dynamics of fecal microbiota and short-chain fatty acids (SCFAs) in different IBS severity groups and study the association with stool pattern, diet, depression, anxiety, and quality of life (QoL). METHODS A longitudinal study was performed, including n = 91 IBS patients and n = 28 matched controls. All participants collected fecal samples for microbiota composition and SCFA analysis and completed validated questionnaires regarding IBS severity, stool pattern, depression, anxiety, and IBS-QoL at two timepoints with four weeks in-between. Diet was assessed at the first timepoint. RESULTS Over time, 36% of IBS patients changed in severity group, and 53% changed in predominant stool pattern. The largest proportion of microbiota variation was explained by the individual (R2 = 70.07%). Microbiota alpha diversity and composition, and SCFAs did not differ between IBS severity groups, nor between IBS and controls. Relative abundances of Bifidobacterium, Terrisporobacter, and Turicibacter consistently differed between IBS and controls, but not between IBS severity groups. Large dynamics over time were observed in the association of microbiota composition with questionnaire data where IBS symptom severity was associated at T1 but not at T2. CONCLUSIONS Fecal microbiota and SCFA signatures were not consistently associated with IBS severity over time, indicating the importance of repeated sampling in IBS research.
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Layunta E, Buey B, Mesonero JE, Latorre E. Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota-Gut-Brain Axis. Front Endocrinol (Lausanne) 2021; 12:748254. [PMID: 34819919 PMCID: PMC8607755 DOI: 10.3389/fendo.2021.748254] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Disruption of the microbiota-gut-brain axis results in a wide range of pathologies that are affected, from the brain to the intestine. Gut hormones released by enteroendocrine cells to the gastrointestinal (GI) tract are important signaling molecules within this axis. In the search for the language that allows microbiota to communicate with the gut and the brain, serotonin seems to be the most important mediator. In recent years, serotonin has emerged as a key neurotransmitter in the gut-brain axis because it largely contributes to both GI and brain physiology. In addition, intestinal microbiota are crucial in serotonin signaling, which gives more relevance to the role of the serotonin as an important mediator in microbiota-host interactions. Despite the numerous investigations focused on the gut-brain axis and the pathologies associated, little is known regarding how serotonin can mediate in the microbiota-gut-brain axis. In this review, we will mainly discuss serotonergic system modulation by microbiota as a pathway of communication between intestinal microbes and the body on the microbiota-gut-brain axis, and we explore novel therapeutic approaches for GI diseases and mental disorders.
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Affiliation(s)
- Elena Layunta
- Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
| | - Berta Buey
- Departamento de Farmacología, Fisiología y Medicina Legal y Forense, Universidad de Zaragoza, Zaragoza, Spain
| | - Jose Emilio Mesonero
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
- Departamento de Farmacología, Fisiología y Medicina Legal y Forense, Universidad de Zaragoza, Zaragoza, Spain
- Instituto Agroalimentario de Aragón—IA2 (Universidad de Zaragoza–CITA), Zaragoza, Spain
| | - Eva Latorre
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
- Instituto Agroalimentario de Aragón—IA2 (Universidad de Zaragoza–CITA), Zaragoza, Spain
- Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain
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Khodabakhsh P, Bazrgar M, Dargahi L, Mohagheghi F, Asgari Taei A, Parvardeh S, Ahmadiani A. Does Alzheimer's disease stem in the gastrointestinal system? Life Sci 2021; 287:120088. [PMID: 34715145 DOI: 10.1016/j.lfs.2021.120088] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/13/2021] [Accepted: 10/21/2021] [Indexed: 02/07/2023]
Abstract
Over the last decades, our knowledge of the key pathogenic mechanisms of Alzheimer's disease (AD) has dramatically improved. Regarding the limitation of current therapeutic strategies for the treatment of multifactorial diseases, such as AD, to be translated into the clinic, there is a growing trend in research to identify risk factors associated with the onset and progression of AD. Here, we review the current literature with a focus on the relationship between gastrointestinal (GI)/liver diseases during the lifespan and the incidence of AD, and discuss the possible mechanisms underlying the link between the diseases. We also aim to review studies evaluating the possible link between the chronic use of the most common GI medications and the future risk of AD development.
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Affiliation(s)
- Pariya Khodabakhsh
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Bazrgar
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leila Dargahi
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mohagheghi
- Institute of Experimental Hematology, Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany
| | - Afsaneh Asgari Taei
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Siavash Parvardeh
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abolhassan Ahmadiani
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Tang HY, Jiang AJ, Wang XY, Wang H, Guan YY, Li F, Shen GM. Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1187. [PMID: 34430628 PMCID: PMC8350700 DOI: 10.21037/atm-21-2779] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 07/14/2021] [Indexed: 12/12/2022]
Abstract
Objective To improve the pathophysiological understanding of irritable bowel syndrome (IBS) by exploring the gut-brain axis. Background Disorders of gut-brain interaction (DGBIs) are gastrointestinal (GI) disorders in which alterations in bowel functions occur. IBS, which is one of the most studied DGBIs, is linked with abdominal distress or pain without obvious structural or biochemical anomalies. Methods The etiology of IBS has not been clearly described but is known to be multifactorial, involving GI motility changes, post-infectious reactivity, visceral hypersensitivity, gut-brain interactions, microbiota dysbiosis, small intestinal bacterial overgrowth, food sensitivity, carbohydrate malabsorption, and intestinal inflammation. Conclusions One of the main features of IBS is the occurrence of structural and functional disruptions in the gut-brain axis, which alter reflective and perceptual nervous system reactions. Herein, we provide a brief summary of this topic. Furthermore, we discuss animal models, which are important in the study of IBS, especially as it is linked with stressors. These animal models cannot fully represent the human disease but serve as important tools for understanding this complicated disorder. In the future, technologies, such as organ-on-a-chip models and metabolomics, will provide novel information regarding the pathophysiology of IBS, which will play an important role in treatment development. Finally, we take a brief glance at how acupuncture treatments may hold potential for patients with IBS.
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Affiliation(s)
- He-Yong Tang
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | - Ai-Juan Jiang
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Xi-Yang Wang
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | - Hao Wang
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Yuan-Yuan Guan
- Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Fei Li
- Department of Rehabilitation, Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Guo-Ming Shen
- School of Integrated Traditional Chinese and Western Medicine, Anhui University of Traditional Chinese Medicine, Hefei, China
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Abstract
Dystonia is a complex neurological movement disorder characterized by involuntary muscle contractions. Increasing studies implicate the microbiome as a possible key susceptibility factor for neurological disorders, but the relationship between the gut microbiota and dystonia remains poorly explored. Here, the gut microbiota of 57 patients with isolated dystonia and 27 age- and environment-matched healthy controls was analyzed by 16S rRNA gene amplicon sequencing. Further, integrative analysis of the gut microbiome and serum metabolome measured by high-performance liquid chromatography-mass spectrometry was performed. No difference in α-diversity was found, while β-diversity was significantly different, with a more heterogeneous community structure among dystonia patients than among controls. The most significant changes in dystonia highlighted an increase in Clostridiales, including Blautia obeum, Dorea longicatena, and Eubacterium hallii, and a reduction in Bacteroides vulgatus and Bacteroides plebeius. The functional analysis revealed that genes related to tryptophan and purine biosynthesis were more abundant in gut microbiota from patients with dystonia, while genes linked to citrate cycle, vitamin B6, and glycan metabolism were less abundant. The evaluation of serum metabolites revealed altered levels of l-glutamic acid, taurine, and d-tyrosine, suggesting changes in neurotransmitter metabolism. The most modified metabolites strongly inversely correlated with the abundance of members belonging to the Clostridiales, revealing the effect of the gut microbiota on neurometabolic activity. This study is the first to reveal gut microbial dysbiosis in patients with isolated dystonia and identified potential links between gut microbiota and serum neurotransmitters, providing new insight into the pathogenesis of isolated dystonia. IMPORTANCE Dystonia is the third most common movement disorder after essential tremor and Parkinson’s disease. However, the cause for the majority of cases is not known. This is the first study so far that reveals significant alterations of gut microbiome and correlates the alteration of serum metabolites with gut dysbiosis in patients with isolated dystonia. We demonstrated a general overrepresentation of Clostridiales and underrepresentation of Bacteroidetes in patients with dystonia in comparison with healthy controls. The functional analysis found that genes related to the biosynthesis of tryptophan, which is the precursor of the neurotransmitter serotonin, were more active in isolated dystonia patients. Altered levels of several serum metabolites were found to be associated with microbial changes, such as d-tyrosine, taurine, and glutamate, indicating differences in neurotransmitter metabolism in isolated dystonia. Integrative analysis suggests that neurotransmitter system dysfunction may be a possible pathway by which the gut microbiome participates in the development of dystonia. The gut microbiome changes provide new insight into the pathogenesis of dystonia, suggesting new potential therapeutic directions.
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Guo J, Lu G, Chen L, Geng H, Wu X, Chen H, Li Y, Yuan M, Sun J, Pei L. Regulation of serum microRNA expression by acupuncture in patients with diarrhea-predominant irritable bowel syndrome. Acupunct Med 2021; 40:34-42. [PMID: 34231397 DOI: 10.1177/09645284211027892] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs. METHODS IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients' serum was re-analyzed for altered expression of the miRNAs by qRT-PCR. RESULTS TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p; P < 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p; P < 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly (P < 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture (P < 0.05). CONCLUSIONS The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms. TRIAL REGISTRATION NUMBER ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry).
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Affiliation(s)
- Jing Guo
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Gao Lu
- School of Second Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Hao Geng
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Xiaoliang Wu
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Hao Chen
- School of Second Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Li
- Gastroenterology Endoscopy Center, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Mengqian Yuan
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Jianhua Sun
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Lixia Pei
- Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6679348. [PMID: 34239591 PMCID: PMC8235976 DOI: 10.1155/2021/6679348] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 06/10/2021] [Indexed: 12/04/2022]
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.
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Wang C, Fang X. Inflammation and Overlap of Irritable Bowel Syndrome and Functional Dyspepsia. J Neurogastroenterol Motil 2021; 27:153-164. [PMID: 33795538 PMCID: PMC8026374 DOI: 10.5056/jnm20175] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 11/23/2020] [Accepted: 11/29/2020] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) and account for a large proportion of consulting patients. These 2 disorders overlap with each other frequently. The pathogenesis of IBS or FD is complicated and multi-factors related, in which infectious or non-infectious inflammation and local or systemic immune response play significant roles. There are few studies focusing on the mechanism of inflammation in patients with overlap syndrome of irritable bowel syndrome and functional dyspepsia (IBS-FD). This review focuses on current advances about the role of inflammation in the pathogenesis of IBS and FD and the possible mechanism of inflammation in IBS-FD.
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Affiliation(s)
- Congzhen Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiucai Fang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Khalilian A, Ahmadimoghaddam D, Saki S, Mohammadi Y, Mehrpooya M. A randomized, double-blind, placebo-controlled study to assess efficacy of mirtazapine for the treatment of diarrhea predominant irritable bowel syndrome. Biopsychosoc Med 2021; 15:3. [PMID: 33536043 PMCID: PMC7860197 DOI: 10.1186/s13030-021-00205-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/27/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ample evidence indicates the efficacy of serotonin type 3 (5-HT3) receptor antagonists in the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Mirtazapine is an atypical antidepressant with a well-known 5-HT3 receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D. METHODS From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (n = 34) or the placebo treatment group (n = 33). Patients started with mirtazapine 15 mg/day at bedtime for one-week; after which the dose was increased to 30 mg/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded. RESULTS All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (P-value = 0.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients' quality of life (P-value = 0.04) and anxiety symptoms (P-value = 0.005). CONCLUSIONS Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated. TRIAL REGISTRATION Trial registration: Registration number at Iranian Registry of Clinical Trials: IRCT20120215009014N311 . Registration date: 2019-10-21.
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Affiliation(s)
- Alireza Khalilian
- Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Davoud Ahmadimoghaddam
- Department of Pharmacology & Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Shiva Saki
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, 6517838678, Iran
| | - Younes Mohammadi
- Modeling of Noncommunicable Diseases Research Center, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Mehrpooya
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, 6517838678, Iran.
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Yaghoubfar R, Behrouzi A, Ashrafian F, Shahryari A, Moradi HR, Choopani S, Hadifar S, Vaziri F, Nojoumi SA, Fateh A, Khatami S, Siadat SD. Modulation of serotonin signaling/metabolism by Akkermansia muciniphila and its extracellular vesicles through the gut-brain axis in mice. Sci Rep 2020; 10:22119. [PMID: 33335202 PMCID: PMC7747642 DOI: 10.1038/s41598-020-79171-8] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 12/04/2020] [Indexed: 12/13/2022] Open
Abstract
Several studies have reported that the host-microbe interactions in the gut modulate the host serotonin or 5-hydroxytryptamine (5-HT) system. Here, we evaluated the effects of Akkermansia muciniphila and its extracellular vesicles (EVs) on genes pertaining to the serotonergic system in the colon and hippocampus of mice. Male C57BL/6J mice were administered viable A. muciniphila and its EVs for 4 weeks. The serotonin levels in the colon, hippocampus, and serum of mice, as well as the human colon carcinoma cells (Caco-2), were measured by ELISA assays. Also, the effects of A. muciniphila and its EVs on the expression of serotonin system genes in the colon and hippocampus were examined. A. muciniphila and its EVs may have a biological effect on the induction of serotonin levels in the colon and hippocampus of mice. Also, EVs increased the serotonin level in the Caco-2 cell line. In contrast, both treatments decreased the serotonin level in the serum. Both the bacterium and its EVs had significant effects on the mRNA expression of genes, involved in serotonin signaling/metabolism in the colon and hippocampus of mice. Moreover, A. muciniphila and its EVs affected the mRNA expression of inflammatory cytokines (Il-10 and Tnf-α) in the colon, however, there is no significant difference in inflammatory cell infiltrate in the histopathology of the colon. The presence of A. muciniphila and its EVs in the gut promotes serotonin concentration, they also affect serotonin signaling/metabolism through the gut-brain axis and may be considered in new therapeutic strategies to ameliorate serotonin-related disorders.
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Affiliation(s)
- Rezvan Yaghoubfar
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Ava Behrouzi
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Fatemeh Ashrafian
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Arefeh Shahryari
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Hamid Reza Moradi
- Department of Basic sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Samira Choopani
- Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran
| | - Shima Hadifar
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Farzam Vaziri
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Ali Nojoumi
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Abolfazl Fateh
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.
| | - Shohreh Khatami
- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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Chen Z, Luo J, Li J, Kim G, Stewart A, Urban JF, Huang Y, Chen S, Wu LG, Chesler A, Trinchieri G, Li W, Wu C. Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis. Immunity 2020; 54:151-163.e6. [PMID: 33220232 DOI: 10.1016/j.immuni.2020.10.014] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 09/13/2020] [Accepted: 10/20/2020] [Indexed: 12/21/2022]
Abstract
The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant environmental challenges. Enterochromaffin (EC) cells, which function as chemosensors on the gut epithelium, are known to translate environmental cues into serotonin (5-HT) production, contributing to intestinal physiology. However, how immune signals participate in gut sensation and neuroendocrine response remains unclear. Interleukin-33 (IL-33) acts as an alarmin cytokine by alerting the system of potential environmental stresses. We here demonstrate that IL-33 induced instantaneous peristaltic movement and facilitated Trichuris muris expulsion. We found that IL-33 could be sensed by EC cells, inducing release of 5-HT. IL-33-mediated 5-HT release activated enteric neurons, subsequently promoting gut motility. Mechanistically, IL-33 triggered calcium influx via a non-canonical signaling pathway specifically in EC cells to induce 5-HT secretion. Our data establish an immune-neuroendocrine axis in calibrating rapid 5-HT release for intestinal homeostasis.
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Affiliation(s)
- Zuojia Chen
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Jialie Luo
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Jian Li
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Girak Kim
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Andy Stewart
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Joseph F Urban
- U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD, USA
| | - Yuefeng Huang
- Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Shan Chen
- Retinal Neurophysiology Section, National Eye Institute, NIH, Bethesda, MD, USA
| | - Ling-Gang Wu
- Synaptic Transmission Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
| | - Alexander Chesler
- Sensory Cells and Circuits Section, National Center for Complementary and Integrative Health, NIH, Bethesda, MD, USA
| | - Giorgio Trinchieri
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Wei Li
- Retinal Neurophysiology Section, National Eye Institute, NIH, Bethesda, MD, USA
| | - Chuan Wu
- Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
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Poolakkandy RR, Menamparambath MM. Transition metal oxide based non‐enzymatic electrochemical sensors: An arising approach for the meticulous detection of neurotransmitter biomarkers. ELECTROCHEMICAL SCIENCE ADVANCES 2020. [DOI: 10.1002/elsa.202000024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD. Life (Basel) 2020; 10:life10100245. [PMID: 33081272 PMCID: PMC7603041 DOI: 10.3390/life10100245] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/08/2020] [Accepted: 10/14/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found.
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Ferreira AI, Garrido M, Castro-Poças F. Irritable Bowel Syndrome: News from an Old Disorder. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2020; 27:255-268. [PMID: 32775547 PMCID: PMC7383263 DOI: 10.1159/000503757] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 09/20/2019] [Indexed: 12/16/2022]
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, which can affect all members of a society, regardless of age, sex, race or socioeconomic status. Because of its high prevalence and chronic nature, it represents a significant economic burden. In fact, these patients have a relevant impairment of their quality of life, which limits their work productivity and daily social activities, especially when it is associated with other disorders, such as anxiety and depression. The diagnosis of IBS relies on symptom-based diagnostic criteria with normal results on a limited number of complementary tests that rule out other possible diagnoses. The aetiology of this condition is incompletely established. However, evidence suggests that it is a multifactorial disorder with several different mechanisms that have been implicated as responsible for the symptoms. Since the treatment strategy is usually based on predominant symptoms and their severity, it is important to recognise the underlying mechanisms in order to successfully relief the visceral pain and altered bowel habits. The aim of this non-systematic review of the literature was to explore the pathophysiology and treatment options of IBS, highlighting the most recent evidence, from the new Rome IV criteria to the new drug armamentarium.
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Affiliation(s)
- Ana Isabel Ferreira
- Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Mónica Garrido
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Fernando Castro-Poças
- Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
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Gao L, Niu X, Niu T, Wang X, Lu X, Hong J, Feng Q, Yang X, González R. Ganjiang granule regulates cecal microflora and serum biochemical components in a rat model of constipation-predominant irritable bowel syndrome. JOURNAL OF TRADITIONAL CHINESE MEDICAL SCIENCES 2020. [DOI: 10.1016/j.jtcms.2020.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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47
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Using Multiple Analytical Platforms to Investigate the Androgen Depletion Effects on Fecal Metabolites in a Mouse Model of Systemic Lupus Erythematosus. J Proteome Res 2019; 19:667-676. [PMID: 31820642 DOI: 10.1021/acs.jproteome.9b00558] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by circulating autoantibodies that deposit in target organs (e.g., kidneys), resulting in chronic inflammation and eventual destruction of the organ. SLE is much more prevalent in females than males in both humans and spontaneous mouse models of lupus, such as NZBxNZW F1 (BWF1) mice. Depleting androgens by castration dramatically increases the susceptibility of BWF1 male to lupus. We compared fecal metabolite profiles of castrated BWF1 (androgen-depleted) male, intact (androgen-replete) male, and female mice. Four analytical platforms were employed to study the profiles of polar metabolites in mouse feces collected from adult BWF1 mice, and a total of 435 metabolites was identified. Of these, the abundance levels of 72 metabolites were significantly different between castrated and intact male groups, and 63 metabolites were different between female and male groups. Pathway analysis indicated that the pathway differences between castrated and intact male mice closely resembled the pathway differences between female and intact male mice, suggesting that low levels of androgens, whether due to depletion (castrated male) or endogenous (female), are associated with multiple fecal metabolomic alterations, which could potentially affect SLE progression. Our findings demonstrate that analyzing fecal metabolites using multiple analytical platforms holds great promise for detecting metabolomic alterations in complex disease model systems.
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5-HT6 receptor antagonism reduces defecation in rat: A potential treatment strategy for irritable bowel syndrome with diarrhea. Eur J Pharmacol 2019; 864:172718. [DOI: 10.1016/j.ejphar.2019.172718] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 10/01/2019] [Accepted: 10/02/2019] [Indexed: 12/14/2022]
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van Thiel IAM, Botschuijver S, de Jonge WJ, Seppen J. Painful interactions: Microbial compounds and visceral pain. Biochim Biophys Acta Mol Basis Dis 2019; 1866:165534. [PMID: 31634534 DOI: 10.1016/j.bbadis.2019.165534] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 08/12/2019] [Accepted: 08/13/2019] [Indexed: 12/18/2022]
Abstract
Visceral pain, characterized by abdominal discomfort, originates from organs in the abdominal cavity and is a characteristic symptom in patients suffering from irritable bowel syndrome, vulvodynia or interstitial cystitis. Most organs in which visceral pain originates are in contact with the external milieu and continuously exposed to microbes. In order to maintain homeostasis and prevent infections, the immune- and nervous system in these organs cooperate to sense and eliminate (harmful) microbes. Recognition of microbial components or products by receptors expressed on cells from the immune and nervous system can activate immune responses but may also cause pain. We review the microbial compounds and their receptors that could be involved in visceral pain development.
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Affiliation(s)
- I A M van Thiel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - S Botschuijver
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - W J de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - J Seppen
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands.
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50
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Abstract
Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
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