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Singh SV, Ganguly R, Jaiswal K, Yadav AK, Kumar R, Pandey AK. Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review. World J Clin Cases 2023; 11:4458-4476. [PMID: 37469740 PMCID: PMC10353503 DOI: 10.12998/wjcc.v11.i19.4458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.
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Affiliation(s)
- Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Aditya Kumar Yadav
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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Forlano R, Sivakumar M, Mullish BH, Manousou P. Gut Microbiota—A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review. Int J Mol Sci 2022; 23:ijms23158307. [PMID: 35955434 PMCID: PMC9368436 DOI: 10.3390/ijms23158307] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 12/03/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.
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Affiliation(s)
- Roberta Forlano
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
| | - Mathuri Sivakumar
- Faculty of Medicine, University of Birmingham, Birmingham B15 2TT, UK;
| | - Benjamin H. Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
| | - Pinelopi Manousou
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
- Correspondence:
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Frausto DM, Forsyth CB, Keshavarzian A, Voigt RM. Dietary Regulation of Gut-Brain Axis in Alzheimer's Disease: Importance of Microbiota Metabolites. Front Neurosci 2021; 15:736814. [PMID: 34867153 PMCID: PMC8639879 DOI: 10.3389/fnins.2021.736814] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that impacts 45 million people worldwide and is ranked as the 6th top cause of death among all adults by the Centers for Disease Control and Prevention. While genetics is an important risk factor for the development of AD, environment and lifestyle are also contributing risk factors. One such environmental factor is diet, which has emerged as a key influencer of AD development/progression as well as cognition. Diets containing large quantities of saturated/trans-fats, refined carbohydrates, limited intake of fiber, and alcohol are associated with cognitive dysfunction while conversely diets low in saturated/trans-fats (i.e., bad fats), high mono/polyunsaturated fats (i.e., good fats), high in fiber and polyphenols are associated with better cognitive function and memory in both humans and animal models. Mechanistically, this could be the direct consequence of dietary components (lipids, vitamins, polyphenols) on the brain, but other mechanisms are also likely to be important. Diet is considered to be the single greatest factor influencing the intestinal microbiome. Diet robustly influences the types and function of micro-organisms (called microbiota) that reside in the gastrointestinal tract. Availability of different types of nutrients (from the diet) will favor or disfavor the abundance and function of certain groups of microbiota. Microbiota are highly metabolically active and produce many metabolites and other factors that can affect the brain including cognition and the development and clinical progression of AD. This review summarizes data to support a model in which microbiota metabolites influence brain function and AD.
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Affiliation(s)
- Dulce M. Frausto
- Rush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
| | - Christopher B. Forsyth
- Rush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
- Department of Medicine, Rush University Medical Center, Chicago, IL, United States
| | - Ali Keshavarzian
- Rush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
- Department of Medicine, Rush University Medical Center, Chicago, IL, United States
- Department of Physiology, Rush University Medical Center, Chicago, IL, United States
| | - Robin M. Voigt
- Rush Medical College, Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
- Department of Medicine, Rush University Medical Center, Chicago, IL, United States
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Bragg M, Freeman EW, Lim HC, Songsasen N, Muletz-Wolz CR. Gut Microbiomes Differ Among Dietary Types and Stool Consistency in the Captive Red Wolf ( Canis rufus). Front Microbiol 2020; 11:590212. [PMID: 33304337 PMCID: PMC7693430 DOI: 10.3389/fmicb.2020.590212] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022] Open
Abstract
Captive management of many wildlife species can be challenging, with individuals displaying health disorders that are not generally described in the wild population. Retrospective studies have identified gastrointestinal (GI) diseases, in particular inflammatory bowel disease (IBD), as the second leading cause of captive adult red wolf (Canis rufus) mortality. Recent molecular studies show that imbalanced gut microbial composition is tightly linked to IBD in the domestic dog. The goal of the present study was to address two main questions: (1) how do red wolf gut microbiomes differ between animals with loose stool consistency, indicative of GI issues, and those with normal stool consistency and (2) how does dietary type relate to stool consistency and red wolf gut microbiomes? Fresh fecal samples were collected from 48 captive wolves housed in eight facilities in the United States and from two wild wolves living in Alligator River National Wildlife Refuge, NC, United States. For each individual, the stool consistency was categorized as loose or normal using a standardized protocol and their diet was categorized as either wild, whole meat, a mix of whole meat and kibble or kibble. We characterized gut microbiome structure using 16S rRNA gene amplicon sequencing. We found that red wolves with a loose stool consistency differed in composition than wolves with normal stool consistency, suggesting a link between GI health and microbiome composition. Diet was not related to stool consistency but did significantly impact gut microbiome composition; gut microbiome composition of wolves fed a kibble diet were significantly different than the gut microbiome composition of wolves fed a mixed, whole meat and wild diet. Findings from this study increase the understanding of the interplay between diet and GI health in the red wolf, a critical piece of information needed to maintain a healthy red wolf population ex situ.
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Affiliation(s)
- Morgan Bragg
- Department of Environmental Science and Policy, George Mason University, Fairfax, VA, United States
- Center for Species Survival, Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA, United States
- Center for Conservation Genomics, Smithsonian Conservation Biology Institute, National Zoological Park, Washington, DC, United States
| | - Elizabeth W. Freeman
- School of Integrative Studies, George Mason University, Fairfax, VA, United States
| | - Haw Chuan Lim
- Department of Biology, George Mason University, Fairfax, VA, United States
| | - Nucharin Songsasen
- Center for Species Survival, Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA, United States
| | - Carly R. Muletz-Wolz
- Center for Conservation Genomics, Smithsonian Conservation Biology Institute, National Zoological Park, Washington, DC, United States
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Herndon CC, Wang YP, Lu CL. Targeting the gut microbiota for the treatment of irritable bowel syndrome. Kaohsiung J Med Sci 2019; 36:160-170. [PMID: 31782606 DOI: 10.1002/kjm2.12154] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 10/20/2019] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.
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Affiliation(s)
- Charles C Herndon
- Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Yen-Po Wang
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Liang Lu
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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