|
1
|
Barbara G, Aziz I, Ballou S, Chang L, Ford AC, Fukudo S, Nurko S, Olano C, Saps M, Sayuk G, Siah KTH, Van Oudenhove L, Simrén M. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol 2025; 22:228-251. [PMID: 39870943 DOI: 10.1038/s41575-024-01033-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.
Collapse
Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Sarah Ballou
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Shin Fukudo
- Department of Psychosomatic Medicine, Japanese Red Cross Ishinomaki Hospital, Research Center for Accelerator and Radioisotope Science, Tohoku University, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Samuel Nurko
- Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA, USA
| | - Carolina Olano
- Gastroenterology Department. Universidad de la República, Montevideo, Uruguay
| | - Miguel Saps
- Division of Gastroenterology, Hepatology, and Nutrition, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Gregory Sayuk
- Gastroenterology Division, Washington University School of Medicine, St. Louis, MO, USA
- St. Louis Veterans Affairs Medical Center, St. Louis, MO, USA
| | - Kewin T H Siah
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
- Consultation-Liaison Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
| |
Collapse
|
|
2
|
Barbaro MR, Bianco F, Cremon C, Marasco G, Stanghellini V, Barbara G. A Probiotic Mixture of Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 Counteracts the Increase in Permeability Induced by the Mucosal Mediators of Irritable Bowel Syndrome by Acting on Zonula Occludens 1. Int J Mol Sci 2025; 26:2656. [PMID: 40141298 PMCID: PMC11942538 DOI: 10.3390/ijms26062656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Irritable Bowel Syndrome (IBS) is a disorder of gut- brain interaction characterized by recurrent abdominal pain associated with altered bowel habits. The therapeutic options for IBS patients include the use of probiotics. The aim of this study was to assess the effect of a multi-strain probiotic made up by Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 (Serobioma, Bromatech s.r.l., Milano, Italy) on an in vitro model of the intestinal epithelial barrier in the presence of mucosal mediators that are released by IBS patients. IBS (n = 28; IBS with predominant diarrhea, IBS-D = 10; IBS with predominant constipation, IBS-C = 9; and IBS with mixed bowel habits, IBS-M = 9) patients, diagnosed according to the Rome IV criteria, and asymptomatic controls (ACs, n = 7) were enrolled. Mucosal mediators that were spontaneously released by colonic biopsies were collected (supernatants). Two doses of Serobioma were tested with/without IBS/AC mediators. RNA was extracted from Caco-2 cells to evaluate the tight junction (TJ) expression. Serobioma (106 CFU/mL) significantly reinforced the Caco-2 monolayer compared to growth medium alone (p < 0.05). IBS supernatants significantly increased Caco-2 paracellular permeability compared to the AC supernatants. The co-incubation of Caco-2 cells with IBS supernatants and Serobioma (106 CFU/mL) avoided the paracellular permeability alterations that were induced by IBS supernatants alone (p < 0.001), and, in particular, IBS-D and IBS-M ones. The co-incubation of Serobioma (106 CFU/mL) and IBS-D supernatants significantly increased ZO-1 expression compared to Caco-2 cells incubated with supernatants alone (p < 0.05), as confirmed via qPCR analyses. Serobioma (106 CFU/mL) counteracts the paracellular permeability changes that are induced by IBS supernatants, in particular IBS-D and IBS-M supernatants, likely modulating ZO-1 expression.
Collapse
Affiliation(s)
- Maria Raffaella Barbaro
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Francesca Bianco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| |
Collapse
|
|
3
|
Yu LCH. Gastrointestinal pathophysiology in long COVID: Exploring roles of microbiota dysbiosis and serotonin dysregulation in post-infectious bowel symptoms. Life Sci 2024; 358:123153. [PMID: 39454992 DOI: 10.1016/j.lfs.2024.123153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/01/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024]
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.
Collapse
Affiliation(s)
- Linda Chia-Hui Yu
- Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
| |
Collapse
|
|
4
|
Gallo A, Murace CA, Corbo MM, Sarlo F, De Ninno G, Baroni S, Fancello G, Masucci L, Covino M, Tosato M, Landi F, Montalto M. Intestinal Inflammation and Permeability in Patients Recovered from SARS-CoV-2 Infection. Dig Dis 2024; 43:1-10. [PMID: 39369712 DOI: 10.1159/000540381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 07/01/2024] [Indexed: 10/08/2024]
Abstract
INTRODUCTION Different works suggest a close link between long COVID gastrointestinal (GI) manifestations and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae. METHODS Eighty-six subjects attending the post-COVID service and recovered from SARS-CoV-2 infection for 6 months were investigated for long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC) and permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and the Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants. RESULTS Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p = 0.03), although remaining quite close to the normal range. No significant differences were shown regarding the assessment of intestinal permeability. By GIQLI, long-term GI sequelae were inversely correlated with quality of life (p = 0.009). CONCLUSION Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post-COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.
Collapse
Affiliation(s)
- Antonella Gallo
- Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
| | - Celeste Ambra Murace
- Department of Geriatrics and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy,
| | - Michela Maria Corbo
- Department of Geriatrics and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy
| | - Francesca Sarlo
- Department of Chemistry, Biochemistry and Clinical Molecular Biology, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
| | - Grazia De Ninno
- Department of Chemistry, Biochemistry and Clinical Molecular Biology, Catholic University of the Sacred Heart, Rome, Italy
| | - Silvia Baroni
- Department of Chemistry, Biochemistry and Clinical Molecular Biology, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Department of Chemistry, Biochemistry and Clinical Molecular Biology, Catholic University of the Sacred Heart, Rome, Italy
| | - Giovanni Fancello
- Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
| | - Luca Masucci
- Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics Catholic University of the Sacred Heart, Rome, Italy
| | - Marcello Covino
- Department of Emergency Medicine, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| | - Matteo Tosato
- Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| | - Francesco Landi
- Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| | - Massimo Montalto
- Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| |
Collapse
|
|
5
|
Ihara E, Manabe N, Ohkubo H, Ogasawara N, Ogino H, Kakimoto K, Kanazawa M, Kawahara H, Kusano C, Kuribayashi S, Sawada A, Takagi T, Takano S, Tomita T, Noake T, Hojo M, Hokari R, Masaoka T, Machida T, Misawa N, Mishima Y, Yajima H, Yamamoto S, Yamawaki H, Abe T, Araki Y, Kasugai K, Kamiya T, Torii A, Nakajima A, Nakada K, Fukudo S, Fujiwara Y, Miwa H, Kataoka H, Nagahara A, Higuchi K. Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023. Digestion 2024; 105:480-497. [PMID: 39197422 PMCID: PMC11633876 DOI: 10.1159/000541121] [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: 06/21/2024] [Accepted: 08/22/2024] [Indexed: 09/01/2024]
Abstract
The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.
Collapse
Affiliation(s)
- Eikichi Ihara
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noriaki Manabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hidenori Ohkubo
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Naotaka Ogasawara
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Haruei Ogino
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Kazuki Kakimoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Motoyori Kanazawa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hidejiro Kawahara
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Chika Kusano
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Shiko Kuribayashi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Akinari Sawada
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Tomohisa Takagi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Shota Takano
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Toshihiko Tomita
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Toshihiro Noake
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Mariko Hojo
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Ryota Hokari
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Tatsuhiro Masaoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Tomohiko Machida
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Noboru Misawa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Yoshiyuki Mishima
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hiroshi Yajima
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Sayuri Yamamoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hiroshi Yamawaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Tatsuya Abe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Yasumi Araki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Kunio Kasugai
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Takeshi Kamiya
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Akira Torii
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Atsushi Nakajima
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Koji Nakada
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Shin Fukudo
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Yasuhiro Fujiwara
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Hiromi Kataoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Akihito Nagahara
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| | - Kazuhide Higuchi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023”, The Japanese Gastroenterological Association, Bunkyo-ku, Japan
| |
Collapse
|
|
6
|
JohnBritto JS, Di Ciaula A, Noto A, Cassano V, Sciacqua A, Khalil M, Portincasa P, Bonfrate L. Gender-specific insights into the irritable bowel syndrome pathophysiology. Focus on gut dysbiosis and permeability. Eur J Intern Med 2024; 125:10-18. [PMID: 38467533 DOI: 10.1016/j.ejim.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 03/05/2024] [Indexed: 03/13/2024]
Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder involving the brain-gut interaction. IBS is characterized by persistent abdominal pain and changes in bowel habits. IBS exerts significant impacts on quality of life and imposes huge economic costs. Global epidemiological data reveal variations in IBS prevalence, both globally and between genders, necessitating comprehensive studies to uncover potential societal and cultural influences. While the exact pathophysiology of IBS remains incompletely understood, the mechanism involves a dysregulation of the brain-gut axis, leading to disturbed intestinal motility, local inflammation, altered intestinal permeability, visceral sensitivity, and gut microbiota composition. We reviewed several gender-related pathophysiological aspects of IBS pathophysiology, by focusing on gut dysbiosis and intestinal permeability. This perspective paves the way to personalized and multidimensional clinical management of individuals with IBS.
Collapse
Affiliation(s)
- Jerlin Stephy JohnBritto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Antonino Noto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Velia Cassano
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Mohamad Khalil
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy.
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| |
Collapse
|
|
7
|
Valibouze C, Dubuquoy C, Chavatte P, Genin M, Maquet V, Modica S, Desreumaux P, Rousseaux C. Chitin-glucan improves important pathophysiological features of irritable bowel syndrome. World J Gastroenterol 2024; 30:2258-2271. [PMID: 38690023 PMCID: PMC11056916 DOI: 10.3748/wjg.v30.i16.2258] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/21/2024] [Accepted: 03/28/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS. AIM To evaluate the roles of CG in visceral analgesia, intestinal inflammation, barrier function, and to develop computational molecular models. METHODS Visceral pain was recorded through colorectal distension (CRD) in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS [15 milligrams (mg)/kilogram (kg)] in 33 Sprague-Dawley rats. Intracolonic pressure was regularly assessed during the 9 wk-experiment (weeks 0, 3, 5, and 7) in animals receiving CG (n = 14) at a human equivalent dose (HED) of 1.5 g/d or 3.0 g/d and compared to negative control (tap water, n = 11) and positive control (phloroglucinol at 1.5 g/d HED, n = 8) groups. The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate (DSS) administered in their drinking water during 14 d. HT-29 cells under basal conditions and after stimulation with lipopolysaccharide (LPS) were treated with CG to evaluate changes in pathways related to analgesia (µ-opioid receptor (MOR), cannabinoid receptor 2 (CB2), peroxisome proliferator-activated receptor alpha, inflammation [interleukin (IL)-10, IL-1b, and IL-8] and barrier function [mucin 2-5AC, claudin-2, zonula occludens (ZO)-1, ZO-2] using the real-time PCR method. Molecular modelling of CG, LPS, lipoteichoic acid (LTA), and phospholipomannan (PLM) was developed, and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations. Data were expressed as the mean ± SEM. RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea, visceral hypersensitivity, or inflammation, as evaluated at histological and molecular levels. In a model of CRD, CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14% after 2 wk of administration (P < 0.01) and reduced inflammation intensity by 50%, resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis. To better reproduce the characteristics of visceral pain in patients with IBS, we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity. CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20% five weeks after colitis induction (P < 0.01). When the CG dosage was increased to 3.0 g/d HED, this analgesic effect surpassed that of the spasmolytic agent phloroglucinol, manifesting more rapidly within 3 wk and leading to a 50% inhibition of pain perception (P < 0.0001). The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved, at least in part, a significant induction of MOR, CB2 receptor, and IL-10, as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8. CG also significantly upregulated barrier-related genes including muc5AC, claudin-2, and ZO-2. Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids, sequestering gram-negative LPS and gram-positive LTA bacterial toxins, as well as PLM in fungi at the lowesr energy conformations. CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.
Collapse
Affiliation(s)
- Caroline Valibouze
- Department of Digestive Surgery and Transplantation, Lille University, Lille 59037, France
| | - Caroline Dubuquoy
- Intestinal Biotech Development, Faculté de Médicine, Lille 59045, France
| | - Philippe Chavatte
- U1286-INFINITE-Institute for Translational Research in Inflammation, Université de Lille, Lille 59000, France
| | - Michaël Genin
- ULR 2694-METRICS, Évaluation des Technologies de santé et des Pratiques Médicales, University of Lille, Lille 59000, France
| | - Veronique Maquet
- KitoZyme SA, Institution Société Anonyme, Zone 2, Parc des Hauts Sarts, Rue de Milmort, Herstal 4040, Belgium
| | - Salvatore Modica
- KitoZyme SA, Institution Société Anonyme, Zone 2, Parc des Hauts Sarts, Rue de Milmort, Herstal 4040, Belgium
| | - Pierre Desreumaux
- Hepato-Gastroenterology Department, Lille University Hospital, Lille 59037, France
| | - Christel Rousseaux
- Intestinal Biotech Development, Faculté de Médicine, Lille 59045, France
| |
Collapse
|
|
8
|
Ye XY, Chen JY, Wu LH, Luo DP, Ye XH, Wu LQ, He XX. Washed microbiota transplantation improves symptoms and intestinal barrier function in patients with functional bowel disorders: a propensity-score matching analysis. BMC Gastroenterol 2024; 24:45. [PMID: 38262980 PMCID: PMC10804514 DOI: 10.1186/s12876-024-03131-z] [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: 03/28/2023] [Accepted: 01/09/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Alterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA). METHODS We conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis. RESULTS PSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093-0.666, P = 0.006) in multivariate Cox regression analysis. CONCLUSION WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.
Collapse
Affiliation(s)
- Xiao-Yan Ye
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Jun-Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Li-Hao Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Dan-Ping Luo
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Xiao-Huo Ye
- Department of Pharmacy, Heyuan Health School, 517000, Heyuan, Guangdong Province, China
| | - Li-Quan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Xing-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China.
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China.
| |
Collapse
|
|
9
|
Alsaady IM. Cryptosporidium and irritable bowel syndrome. Trop Parasitol 2024; 14:8-15. [PMID: 38444793 PMCID: PMC10911187 DOI: 10.4103/tp.tp_10_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 10/16/2023] [Accepted: 10/22/2023] [Indexed: 03/07/2024] Open
Abstract
Cryptosporidium is an apicomplexan parasite that causes gastrointestinal disease in a wide variety of hosts and is associated with waterborne outbreaks. Nonetheless, the parasite is underdiagnosed. Cryptosporidium has been proposed as an etiological cause of irritable bowel syndrome (IBS) in several studies. However, the exact mechanism of pathogenesis is unknown, and no direct link has been discovered. This review will discuss several parasite-induced modifications, such as immunological, microbiome, and metabolite modifications, as well as their interactions. To summarize, Cryptosporidium causes low inflammation, dysbiosis, and unbalanced metabolism, which leads to a lack of homeostasis in the intestine in a comparable pattern to postinfectious IBS.
Collapse
Affiliation(s)
- Isra Mohammad Alsaady
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahad Medical Research Centre, Special Infectious Agents Unit, Jeddah, Saudi Arabia
| |
Collapse
|
|
10
|
Park JH, Kang SH, Kim JS, Moon HS, Sung JK, Jeong HY. Contribution of sex and gender roles to the incidence of post-infectious irritable bowel syndrome in a prospective study. Sci Rep 2023; 13:19467. [PMID: 37945663 PMCID: PMC10636197 DOI: 10.1038/s41598-023-45300-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/18/2023] [Indexed: 11/12/2023] Open
Abstract
Post-infectious irritable bowel syndrome (PI-IBS) occurs in about 10% of cases following gastroenteritis. The incidence of IBS is higher in females. However, it is not clear whether this is due to biological or psychosocial factors. We aimed to investigate the influence of gender roles on the incidence of PI-IBS, alongside traditional risk factors. Our study included 231 patients diagnosed with gastroenteritis who were hospitalized and treated with antibiotics between 2018 and 2021. The Korean Sex Role Inventory-Short Form (KSRI-SF), based on the Bem Sex Role Inventory (BSRI) was used to categorize patients (androgynous, masculine, feminine, and undifferentiated types). Six months after treatment, we conducted a telephone survey to confirm the presence of PI-IBS using the ROME IV criteria. Among the patients, 43.3% were female, and the mean age was 43.67 ± 16.09 years. After 6 months, 34 patients developed PI-IBS. Univariate analysis revealed that younger age, female sex, KSRI-SF undifferentiated type, and longer duration of antibiotic use independently influenced the occurrence of PI-IBS. Multivariate analysis showed that PI-IBS was associated with the KSRI-SF undifferentiated type and higher C-reactive protein (CRP) levels. Our study showed that the KSRI-SF undifferentiated type and high CRP levels at initial infection were associated with PI-IBS.
Collapse
Affiliation(s)
- Jae Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong, South Korea
- Chungnam National University School of Medicine, Daejeon, South Korea
| | - Sun Hyung Kang
- Chungnam National University School of Medicine, Daejeon, South Korea.
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea.
| | - Ju Seok Kim
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong, South Korea
- Chungnam National University School of Medicine, Daejeon, South Korea
| | - Hee Seok Moon
- Chungnam National University School of Medicine, Daejeon, South Korea
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Jae Kyu Sung
- Chungnam National University School of Medicine, Daejeon, South Korea
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Hyun Yong Jeong
- Chungnam National University School of Medicine, Daejeon, South Korea
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| |
Collapse
|
|
11
|
Brant BJA, Yu Y, Omar AA, Jaramillo Polanco JO, Lopez Lopez CD, Jiménez Vargas NN, Tsang Q, McDonell A, Takami K, Reed DE, Lomax AE, Vanner SJ, Tuck CJ. Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain. Neurogastroenterol Motil 2023; 35:e14596. [PMID: 37248774 DOI: 10.1111/nmo.14596] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 01/24/2023] [Accepted: 04/03/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND Monosodium glutamate (MSG) has been identified as a trigger of abdominal pain in irritable bowel syndrome (IBS), but the mechanism is unknown. This study examined whether MSG causes visceral hypersensitivity using a water-avoidance stress (WAS) mouse model of visceral pain. METHODS Mice were divided into four groups receiving treatment for 6 days: WAS + MSG gavage, WAS + saline gavage, sham-WAS + MSG gavage, and sham-WAS + saline gavage. The acute effects of intraluminal administration of 10 μM MSG on jejunal extrinsic afferent nerve sensitivity to distension (0-60 mmHg) were examined using ex vivo extracellular recordings. MSG was also applied directly to jejunal afferents from untreated mice. Glutamate concentration was measured in serum, and in the serosal compartment of Ussing chambers following apical administration. KEY RESULTS Acute intraluminal MSG application increased distension responses of jejunal afferent nerves from mice exposed to WAS + MSG. This effect was mediated by wide dynamic range and high-threshold units at both physiologic and noxious pressures (10-60 mmHg, p < 0.05). No effect of MSG was observed in the other groups, or when applied directly to the jejunal afferent nerves. Serum glutamate was increased in mice exposed to WAS + MSG compared to sham-WAS + saline, and serosal glutamate increased using WAS tissue (p = 0.0433). CONCLUSIONS AND INFERENCES These findings demonstrate that repeated exposure to MSG in mice leads to sensitization of jejunal afferent nerves to acute ex vivo exposure to MSG. This may contribute to visceral hypersensitivity reported in response to MSG in patients with IBS.
Collapse
Affiliation(s)
- Bailey J A Brant
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Yang Yu
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Amal Abu Omar
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Cintya D Lopez Lopez
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Quentin Tsang
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Abby McDonell
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Kaede Takami
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - David E Reed
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Alan E Lomax
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Stephen J Vanner
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Caroline J Tuck
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia
| |
Collapse
|
|
12
|
Varani J, McClintock SD, Nadeem DM, Harber I, Zeidan D, Aslam MN. A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids. Front Cell Dev Biol 2023; 11:1132905. [PMID: 37476158 PMCID: PMC10354648 DOI: 10.3389/fcell.2023.1132905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 06/21/2023] [Indexed: 07/22/2023] Open
Abstract
Introduction: Ulcerative colitis is a chronic inflammatory condition, and continuous inflammatory stimulus may lead to barrier dysfunction. The goal of this study was to assess barrier proteomic expression by a red algae-derived multi-mineral intervention in the absence or presence of pro-inflammatory insult. Methods: Human colon organoids were maintained in a control culture medium alone or exposed to lipopolysaccharide with a combination of three pro-inflammatory cytokines [tumor necrosis factor-α, interleukin-1β and interferon-γ (LPS-cytokines)] to mimic the environment in the inflamed colon. Untreated organoids and those exposed to LPS-cytokines were concomitantly treated for 14 days with a multi-mineral product (Aquamin®) that has previously been shown to improve barrier structure/function. The colon organoids were subjected to proteomic analysis to obtain a broad view of the protein changes induced by the two interventions alone and in combination. In parallel, confocal fluorescence microscopy, tissue cohesion and transepithelial electrical resistance (TEER) measurements were used to assess barrier structure/function. Results: The LPS-cytokine mix altered the expression of multiple proteins that influence innate immunity and promote inflammation. Several of these were significantly decreased with Aquamin® alone but only a modest decrease in a subset of these proteins was detected by Aquamin® in the presence of LPS-cytokines. Among these, a subset of inflammation-related proteins including fibrinogen-β and -γ chains (FGB and FGG), phospholipase A2 (PLA2G2A) and SPARC was significantly downregulated in the presence of Aquamin® (alone and in combination with LPS-cytokines); another subset of proteins with anti-inflammatory, antioxidant or anti-microbial activity was upregulated by Aquamin® treatment. When provided alone, Aquamin® strongly upregulated proteins that contribute to barrier formation and tissue strength. Concomitant treatment with LPS-cytokines did not inhibit barrier formation in response to Aquamin®. Confocal microscopy also displayed increased expression of desmoglein-2 (DSG2) and cadherin-17 (CDH17) with Aquamin®, either alone or in the presence of the pro-inflammatory stimulus. Increased cohesion and TEER with Aquamin® (alone or in the presence of LPS-cytokines) indicates improved barrier function. Conclusion: Taken together, these findings suggest that multi-mineral intervention (Aquamin®) may provide a novel approach to combating inflammation in the colon by improving barrier structure/function as well as by directly altering the expression of certain pro-inflammatory proteins.
Collapse
Affiliation(s)
| | | | | | | | | | - Muhammad N. Aslam
- Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, United States
| |
Collapse
|
|
13
|
Fu Y, Waghray N, Fass R, Song G. Diagnostic Implications of Irritable Bowel Syndrome Is an Independent Risk Factor for Undergoing Surgical Interventions in Patients with Inflammatory Bowel Disease. Diagnostics (Basel) 2023; 13:diagnostics13111901. [PMID: 37296752 DOI: 10.3390/diagnostics13111901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 05/18/2023] [Accepted: 05/27/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can present with overlapping symptoms, making diagnosis and management challenging. Patients with IBD in remission may continue to experience IBS symptoms. Patients with IBS were found to have a disproportionately higher prevalence of abdominal and pelvic surgeries than the general population. AIMS The aim of this study was to determine whether IBS is a risk factor for undergoing surgical interventions in patients with IBD and explore the diagnostic implications of these findings. METHODS A population-based cohort analysis was performed using TriNetX. Patients with Crohn's disease + IBS (CD + IBS) and ulcerative colitis + IBS (UC + IBS) were identified. The control groups consisted of patients with CD or UC alone without IBS. The main outcome was to compare the risks of undergoing surgical interventions between the cohorts. The secondary outcomes were to compare the risks of developing gastrointestinal symptoms and IBD-related complications between the cohorts. RESULTS Patients with IBD who subsequently developed IBS were more likely to experience gastrointestinal symptoms than those without IBS (p < 0.0001). Patients with concomitant IBD and IBS were more likely to develop IBD-related complications, including perforation of the intestine, gastrointestinal bleeding, colon cancer, and abdominal abscess (p < 0.05). Patients with concomitant IBD and IBS were more likely to undergo surgical interventions than patients without IBS, including colectomy, appendectomy, cholecystectomy, exploratory laparotomy, and hysterectomy (p < 0.05). CONCLUSIONS IBS appears to be an independent risk factor for patients with IBD to develop IBD-related complications and undergo surgical interventions. Patients with concomitant IBD and IBS could represent a unique subgroup of IBD patients with more severe symptoms, highlighting the importance of accurate diagnosis and management in this population.
Collapse
Affiliation(s)
- Yuhan Fu
- Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
| | - Nisheet Waghray
- Department of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
| | - Ronnie Fass
- Department of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
| | - Gengqing Song
- Department of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
| |
Collapse
|
|
14
|
Horowitz A, Chanez-Paredes SD, Haest X, Turner JR. Paracellular permeability and tight junction regulation in gut health and disease. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00766-3. [PMID: 37186118 PMCID: PMC10127193 DOI: 10.1038/s41575-023-00766-3] [Citation(s) in RCA: 225] [Impact Index Per Article: 112.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2023] [Indexed: 05/17/2023]
Abstract
Epithelial tight junctions define the paracellular permeability of the intestinal barrier. Molecules can cross the tight junctions via two distinct size-selective and charge-selective paracellular pathways: the pore pathway and the leak pathway. These can be distinguished by their selectivities and differential regulation by immune cells. However, permeability increases measured in most studies are secondary to epithelial damage, which allows non-selective flux via the unrestricted pathway. Restoration of increased unrestricted pathway permeability requires mucosal healing. By contrast, tight junction barrier loss can be reversed by targeted interventions. Specific approaches are needed to restore pore pathway or leak pathway permeability increases. Recent studies have used preclinical disease models to demonstrate the potential of pore pathway or leak pathway barrier restoration in disease. In this Review, we focus on the two paracellular flux pathways that are dependent on the tight junction. We discuss the latest evidence that highlights tight junction components, structures and regulatory mechanisms, their impact on gut health and disease, and opportunities for therapeutic intervention.
Collapse
Affiliation(s)
- Arie Horowitz
- UNIROUEN, INSERM U1245, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France
| | - Sandra D Chanez-Paredes
- Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Xenia Haest
- Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jerrold R Turner
- Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
15
|
Stillhart C, Asteriadis A, Bocharova E, Eksteen G, Harder F, Kusch J, Tzakri T, Augustijns P, Matthys C, Vertzoni M, Weitschies W, Reppas C. The impact of advanced age on gastrointestinal characteristics that are relevant to oral drug absorption: An AGePOP review. Eur J Pharm Sci 2023; 187:106452. [PMID: 37098371 DOI: 10.1016/j.ejps.2023.106452] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/12/2023] [Accepted: 04/21/2023] [Indexed: 04/27/2023]
Abstract
The purpose of this review is to summarize the current knowledge on three physiological determinants of oral drug absorption, i.e., gastric emptying, volumes and composition of luminal fluids, and intestinal permeability, in the advanced age population, so that potential knowledge gaps and directions for further research efforts are identified. Published data on gastric emptying rates in older people are conflicting. Also, there are significant knowledge gaps, especially on gastric motility and emptying rates of drugs and of non-caloric fluids. Compared with younger adults, volumes of luminal contents seem to be slightly smaller in older people. Our understanding on the impact of advanced age on luminal physicochemical characteristics is, at best, very limited, whereas the impact of (co)morbidities and geriatric syndromes in the advanced age population has not been addressed to date. The available literature on the effect of advanced age on intestinal permeability is limited, and should be approached with caution, primarily due to the limitations of the experimental methodologies used.
Collapse
Affiliation(s)
| | - Adam Asteriadis
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Ekaterina Bocharova
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Gabriel Eksteen
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Fritz Harder
- Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium
| | - Jonas Kusch
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodora Tzakri
- Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, University of Greifswald, Germany
| | - Patrick Augustijns
- Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium
| | - Christophe Matthys
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Maria Vertzoni
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - Werner Weitschies
- Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport, University of Greifswald, Germany
| | - Christos Reppas
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
| |
Collapse
|
|
16
|
Sharma S, Kumar S, Sajjad S, Sharma S. Probiotics in Irritable Bowel Syndrome: A Review Article. Cureus 2023; 15:e36565. [PMID: 37095805 PMCID: PMC10122169 DOI: 10.7759/cureus.36565] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 03/23/2023] [Indexed: 04/26/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a persistent set of symptoms that reduces one's goodness of life. The treatment of these people is usually focused on reducing the symptoms caused by the condition. This article examines the function of probiotics in alleviating symptoms in IBS patients. The goal of studying the impact of probiotics on IBS patients is to research the changes they cause to the gut microbiota, which may be beneficial in preventing and treating such diseases over time. This article also discusses the pathophysiology, diagnostic standards, therapeutic modalities, probiotic sources, and therapeutic relevance for IBS patients.
Collapse
Affiliation(s)
- Shatakshi Sharma
- Department of Medicine, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, IND
| | - Sunil Kumar
- Department of Medicine, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, IND
| | - Sheeral Sajjad
- Department of Medicine, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, IND
| | - Samriddhi Sharma
- Department of Medicine, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, IND
| |
Collapse
|
|
17
|
Chen Q, Zhang H, Sun CY, He QY, Zhang RR, Luo BF, Zhou ZH, Chen XF. Evaluation of two laboratory model methods for diarrheal irritable bowel syndrome. Mol Med 2023; 29:5. [PMID: 36635623 PMCID: PMC9837933 DOI: 10.1186/s10020-022-00599-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 12/27/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. METHODS The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. RESULTS Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1β, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. CONCLUSION In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.
Collapse
Affiliation(s)
- Qian Chen
- Evidence-Based Medicine Research Centre, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Hua Zhang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Chang-Yue Sun
- Evidence-Based Medicine Research Centre, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Qing-Ying He
- grid.411304.30000 0001 0376 205XChengdu University of Traditional Chinese Medicine, Chengdu, 611137 China
| | - Rui-Rong Zhang
- Department of Food Nutrition and Safety, College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Bin-Fei Luo
- Evidence-Based Medicine Research Centre, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Zi-Hao Zhou
- Evidence-Based Medicine Research Centre, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| | - Xiao-Fan Chen
- Evidence-Based Medicine Research Centre, Jiangxi University of Chinese Medicine, Nanchang, 330004 Jiangxi China
| |
Collapse
|
|
18
|
Awad K, Barmeyer C, Bojarski C, Nagel O, Lee IFM, Schweiger MR, Schulzke JD, Bücker R. Impaired Intestinal Permeability of Tricellular Tight Junctions in Patients with Irritable Bowel Syndrome with Mixed Bowel Habits (IBS-M). Cells 2023; 12:236. [PMID: 36672170 PMCID: PMC9856377 DOI: 10.3390/cells12020236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/27/2022] [Accepted: 01/03/2023] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The underlying pathophysiology of irritable bowel syndrome (IBS) is still unclear. Our aim was to investigate the pathophysiological mechanisms of diarrhea, constipation, and antigen uptake in mixed-type IBS (IBS-M). METHODS Colonoscopic biopsies were obtained from IBS-M patients. Epithelial transport and barrier function of colonic mucosae were characterized in Ussing chambers using impedance spectroscopy. Mucosal permeability to macromolecules was measured. Western blotting for tight junction (TJ) proteins was performed and their subcellular localization was visualized by confocal microscopy. RNA-sequencing was performed for gene expression and signaling pathway analysis. RESULTS In IBS-M, epithelial resistance and ENaC-dependent sodium absorption were unchanged, while short-circuit current reflecting chloride secretion was reduced. Concomitantly, epithelial permeability for fluorescein and FITC-dextran-4000 increased. TJ protein expression of occludin decreased, whereas claudins were unaltered. Confocal microscopy revealed the de-localization of tricellulin from tricellular TJs. Involved pathways were detected as proinflammatory cytokine pathways, LPS, PGE2, NGF, and vitamin D. CONCLUSIONS Decreased anion secretion explains constipation in IBS-M, while ion permeability and sodium absorption were unaltered. Reduced occludin expression resulted in the delocalization of tricellulin from the tricellular TJ, leading to increased macromolecular permeability that contributes to antigen influx into the mucosa and perpetuates a low-grade inflammatory process.
Collapse
Affiliation(s)
- Karem Awad
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Christian Barmeyer
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Christian Bojarski
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Oliver Nagel
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - In-Fah M. Lee
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Michal R. Schweiger
- Institute for Translational Epigenetics, Medical Faculty, University of Cologne, 50931 Cologne, Germany
| | - Jörg-Dieter Schulzke
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Roland Bücker
- Clinical Physiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| |
Collapse
|
|
19
|
Sanz Morales P, Wijeyesekera A, Robertson MD, Jackson PPJ, Gibson GR. The Potential Role of Human Milk Oligosaccharides in Irritable Bowel Syndrome. Microorganisms 2022; 10:microorganisms10122338. [PMID: 36557589 PMCID: PMC9781515 DOI: 10.3390/microorganisms10122338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Irritable Bowel Syndrome (IBS) is the most common gastrointestinal (GI) disorder in Western populations and therefore a major public health/economic concern. However, despite extensive research, psychological and physiological factors that contribute to the aetiology of IBS remain poorly understood. Consequently, clinical management of IBS is reduced to symptom management through various suboptimal options. Recent evidence has suggested human milk oligosaccharides (HMOs) as a potential therapeutic option for IBS. Here, we review literature concerning the role of HMOs in IBS, including data from intervention and in vitro trials. HMO supplementation shows promising results in altering the gut microbiota and improving IBS symptoms, for instance by stimulating bifidobacteria. Further research in adults is required into HMO mechanisms, to confirm the preliminary results available to date and recommendations of HMO use in IBS.
Collapse
Affiliation(s)
- Patricia Sanz Morales
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AH, UK
- Correspondence: ; Tel.: +44-7843865554
| | - Anisha Wijeyesekera
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AH, UK
| | - Margaret Denise Robertson
- Department of Nutritional Sciences, Faculty of Health & Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
| | - Peter P. J. Jackson
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AH, UK
| | - Glenn R. Gibson
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AH, UK
| |
Collapse
|
|
20
|
McHarg AS, Leach S. The role of the gut microbiome in paediatric irritable bowel syndrome. AIMS Microbiol 2022; 8:454-469. [PMID: 36694592 PMCID: PMC9834077 DOI: 10.3934/microbiol.2022030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/10/2022] [Accepted: 11/14/2022] [Indexed: 11/23/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common and disabling condition in children. The pathophysiology of IBS is thought to be multifactorial but remains incompletely understood. There is growing evidence implicating the gut microbiome in IBS. Intestinal dysbiosis has been demonstrated in paediatric IBS cohorts; however, no uniform or consistent pattern has been identified. The exact mechanisms by which this dysbiosis contributes to IBS symptoms remain unknown. Available evidence suggests the imbalance produces a functional dysbiosis, with altered production of gases and metabolites that interact with the intestinal wall to cause symptoms, and enrichment or depletion of certain metabolic pathways. Additional hypothesised mechanisms include increased intestinal permeability, visceral hypersensitivity and altered gastrointestinal motility; however, these remain speculative in paediatric patients, with studies limited to animal models and adult populations. Interaction between dietary components and intestinal microbiota, particularly with fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), has drawn increasing attention. FODMAPs have been found to trigger and worsen IBS symptoms. This is thought to be related to products of their fermentation by a dysbiotic microbial population, although this remains to be proven. A low-FODMAP diet has shown promising success in ameliorating symptoms in some but not all patients. There remains much to be discovered about the role of the dysbiotic microbiome in paediatric IBS.
Collapse
Affiliation(s)
- Alexandra S McHarg
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia,Westfield Research Laboratories, Sydney Children's Hospital, Randwick, NSW, Australia,* Correspondence:
| | - Steven Leach
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia,Westfield Research Laboratories, Sydney Children's Hospital, Randwick, NSW, Australia
| |
Collapse
|
|
21
|
Bootz-Maoz H, Pearl A, Melzer E, Malnick S, Sharon E, Bennet Y, Tsentsarevsky R, Abuchatzera S, Amidror S, Aretz E, Azriel S, Gam Ze Letova C, Naama M, Shoval I, Yaron O, Karako-Lampert S, Bel S, Yissachar N. Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome. Cell Rep 2022; 41:111657. [DOI: 10.1016/j.celrep.2022.111657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 07/25/2022] [Accepted: 10/21/2022] [Indexed: 11/17/2022] Open
|
|
22
|
Guo F, Liu D, Zhou Y, Yu Y, Xu Y, Zou Y, Li C, Zhang F, Yu Z. Pharmacokinetic study of single and multiple oral administration of glutamine in healthy Beagles. Front Pharmacol 2022; 13:1014474. [PMID: 36249805 PMCID: PMC9563617 DOI: 10.3389/fphar.2022.1014474] [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: 08/08/2022] [Accepted: 09/12/2022] [Indexed: 11/21/2022] Open
Abstract
Glutamine is an amino acid that is mainly used for the treatment of gastrointestinal diseases in clinic, but there is a lack of such medicine in veterinary clinic, and its research in dogs has never been seen. This study aimed to investigate the pharmacokinetics of single and multiple administration of glutamine (Gln) tablets in Beagles. Twenty-four healthy Beagles were randomly selected for the pharmacokinetic study of a single dose of low (120 mg/kg), medium (240 mg/kg), and high (360 mg/kg) Gln tablets. After 7 days of washout period, six Beagles in the medium group were selected for a multiple-dose pharmacokinetic study, 240 mg/kg twice a day for 7 days. The Gln concentration in plasma was determined by a validated UPLC-MS/MS method. The results of single oral administration of different doses of Gln tablets showed that Cmax, AUC0→t, AUC0→∝ had a certain linear relationship with the dosage. T-tests were performed for single and multiple administration of Tmax, Cmax, t1/2λz, AUC0→t, and AUC0→∝, and the results showed no significant differences (p > 0.05). Therefore, Gln tablets were absorbed quickly by oral administration, and there was no accumulation in Beagles after 7 days of administration.
Collapse
|
|
23
|
Cuddihey H, Cavin JB, Keenan CM, Wallace LE, Vemuri K, Makriyannis A, MacNaughton WK, Sharkey KA. Role of CB 1 receptors in the acute regulation of small intestinal permeability: effects of high-fat diet. Am J Physiol Gastrointest Liver Physiol 2022; 323:G219-G238. [PMID: 35787179 PMCID: PMC9394780 DOI: 10.1152/ajpgi.00341.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 01/31/2023]
Abstract
The endocannabinoid system of the gastrointestinal tract is involved in the control of intestinal barrier function. Whether the cannabinoid 1 (CB1) receptor is expressed on the intestinal epithelium and acutely regulates barrier function has not been determined. Here, we tested the hypothesis that ligands of the CB1 receptor acutely modulate small intestinal permeability and that this is associated with altered distribution of tight junction proteins. We examined the acute effects of CB1 receptor ligands on small intestinal permeability both in chow-fed and 2-wk high-fat diet (HFD)-fed mice using Ussing chambers. We assessed the distribution of CB1 receptor and tight junction proteins using immunofluorescence and the expression of CB1 receptor using PCR. A low level of CB1 expression was found on the intestinal epithelium. CB1 receptor was highly expressed on enteric nerves in the lamina propria. Neither the CB1/CB2 agonist CP55,940 nor the CB1 neutral antagonist AM6545 altered the flux of 4kDa FITC dextran (FD4) across the jejunum or ileum of chow-fed mice. Remarkably, both CP55,940 and AM6545 reduced FD4 flux across the jejunum and ileum in HFD-fed mice that have elevated baseline intestinal permeability. These effects were absent in CB1 knockout mice. CP55,940 reduced the expression of claudin-2, whereas AM6545 had little effect on claudin-2 expression. Neither ligand altered the expression of ZO-1. Our data suggest that CB1 receptor on the intestinal epithelium regulates tight junction protein expression and restores barrier function when it is increased following exposure to a HFD for 2 wk.NEW & NOTEWORTHY The endocannabinoid system of the gastrointestinal tract regulates homeostasis by acting as brake on motility and secretion. Here we show that when exposed to a high fat diet, intestinal permeability is increased and activation of the CB1 receptor on the intestinal epithelium restores barrier function. This work further highlights the role of the endocannabinoid system in regulating intestinal homeostasis when it is perturbed.
Collapse
Affiliation(s)
- Hailey Cuddihey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jean-Baptiste Cavin
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Inflammation Research Network, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Catherine M Keenan
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Laurie E Wallace
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kiran Vemuri
- Center for Drug Discovery, Northeastern University, Boston, Massachusetts
- Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts
| | - Alexandros Makriyannis
- Center for Drug Discovery, Northeastern University, Boston, Massachusetts
- Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts
| | - Wallace K MacNaughton
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Inflammation Research Network, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Keith A Sharkey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| |
Collapse
|
|
24
|
Gut Non-Bacterial Microbiota: Emerging Link to Irritable Bowel Syndrome. Toxins (Basel) 2022; 14:toxins14090596. [PMID: 36136534 PMCID: PMC9503233 DOI: 10.3390/toxins14090596] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/18/2022] [Accepted: 08/25/2022] [Indexed: 11/20/2022] Open
Abstract
As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.
Collapse
|
|
25
|
Hone Lopez S, Jalving M, Fehrmann RS, Nagengast WB, de Vries EG, de Haan JJ. The gut wall’s potential as a partner for precision oncology in immune checkpoint treatment. Cancer Treat Rev 2022; 107:102406. [DOI: 10.1016/j.ctrv.2022.102406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/29/2022] [Accepted: 05/01/2022] [Indexed: 11/02/2022]
|
|
26
|
Wiley JW, Higgins GA, Hong S. Chronic psychological stress alters gene expression in rat colon epithelial cells promoting chromatin remodeling, barrier dysfunction and inflammation. PeerJ 2022; 10:e13287. [PMID: 35509963 PMCID: PMC9059753 DOI: 10.7717/peerj.13287] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 03/28/2022] [Indexed: 01/25/2023] Open
Abstract
Chronic stress is commonly associated with enhanced abdominal pain (visceral hypersensitivity), but the cellular mechanisms underlying how chronic stress induces visceral hypersensitivity are poorly understood. In this study, we examined changes in gene expression in colon epithelial cells from a rat model using RNA-sequencing to examine stress-induced changes to the transcriptome. Following chronic stress, the most significantly up-regulated genes included Atg16l1, Coq10b, Dcaf13, Nat2, Ptbp2, Rras2, Spink4 and down-regulated genes including Abat, Cited2, Cnnm2, Dab2ip, Plekhm1, Scd2, and Tab2. The primary altered biological processes revealed by network enrichment analysis were inflammation/immune response, tissue morphogenesis and development, and nucleosome/chromatin assembly. The most significantly down-regulated process was the digestive system development/function, whereas the most significantly up-regulated processes were inflammatory response, organismal injury, and chromatin remodeling mediated by H3K9 methylation. Furthermore, a subpopulation of stressed rats demonstrated very significantly altered gene expression and transcript isoforms, enriched for the differential expression of genes involved in the inflammatory response, including upregulation of cytokine and chemokine receptor gene expression coupled with downregulation of epithelial adherens and tight junction mRNAs. In summary, these findings support that chronic stress is associated with increased levels of cytokines and chemokines, their downstream signaling pathways coupled to dysregulation of intestinal cell development and function. Epigenetic regulation of chromatin remodeling likely plays a prominent role in this process. Results also suggest that super enhancers play a primary role in chronic stress-associated intestinal barrier dysfunction.
Collapse
Affiliation(s)
- John W. Wiley
- Department of Internal Medicine, University of Michigan - Ann Arbor, Ann Arbor, MI, United States of America
| | - Gerald A. Higgins
- Department of Computational Medicine and Bioinformatics, University of Michigan - Ann Arbor, Ann Arbor, MI, United States of America
| | - Shuangsong Hong
- Department of Internal Medicine, University of Michigan - Ann Arbor, Ann Arbor, MI, United States of America
| |
Collapse
|
|
27
|
Inczefi O, Bacsur P, Resál T, Keresztes C, Molnár T. The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease. Front Nutr 2022; 9:718710. [PMID: 35548572 PMCID: PMC9082752 DOI: 10.3389/fnut.2022.718710] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 02/22/2022] [Indexed: 01/09/2023] Open
Abstract
The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.
Collapse
Affiliation(s)
- Orsolya Inczefi
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Péter Bacsur
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Resál
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Csilla Keresztes
- Department for Medical Communication and Translation Studies, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Molnár
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary,*Correspondence: Tamás Molnár,
| |
Collapse
|
|
28
|
Magnus Y, BouSaba J, Sannaa W, McKinzie S, Busciglio I, Camilleri M. Bile Acid Diarrhea Is Associated With Increased Intestinal Permeability Compared With Irritable Bowel Syndrome-Diarrhea. Gastroenterology 2022; 162:1343-1345.e1. [PMID: 34922946 PMCID: PMC8934275 DOI: 10.1053/j.gastro.2021.12.243] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/02/2021] [Accepted: 12/12/2021] [Indexed: 01/14/2023]
Affiliation(s)
| | | | | | | | | | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
| |
Collapse
|
|
29
|
Zhao L, Ren P, Wang M, Wang J, He X, Gu J, Lu Y, Wu Y, Liu J, Wang L, Li H. Changes in intestinal barrier protein expression and intestinal flora in a rat model of visceral hypersensitivity. Neurogastroenterol Motil 2022; 34:e14299. [PMID: 34821442 DOI: 10.1111/nmo.14299] [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: 01/26/2021] [Revised: 08/30/2021] [Accepted: 11/10/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Destruction of the intestinal mucosal barrier and visceral hypersensitivity are main pathogenesis of irritable bowel syndrome (IBS). The study aimed to establish a rat model of visceral hypersensitivity and explore mechanisms involved the changes of the intestinal barrier protein expression and intestinal flora. METHODS A rat model of visceral hypersensitivity was established and evaluated using abdominal withdrawal reflex (AWR) scores, colonic paracellular permeability, and gastrointestinal motility. The expression of tight junction proteins, aquaporin proteins (AQPs), phosphorylated ERK, and proteinase-activated receptor-2 (PAR-2) was determined. The intestinal microflora was evaluated by high-throughput sequencing of the 16S rRNA gene. KEY RESULTS In model rats, AWR score and fecal water content were significantly increased, gastrointestinal motilities were disorder and characterized by an inhibition of gastric motility and an enhancement of small intestinal and colonic movement. The expressions of colonic occludin, ZO-1, AQP3, and AQP8 were decreased but claudin-2 and claudin-4 were markedly increased. Imbalance of intestinal flora appeared and showed an obvious decrease of Lactobacillus and an increase of Clostridiales_bacterium. Additionally, the total serine protease activity in feces, the expressions of PAR2 and phosphorylated ERK in the colon tissues were increased significantly. CONCLUSION AND INFERENCES The model rats of visceral hypersensitivity possess the decreased expression of occludin, ZO-1, AQP3, AQP8, and the increased expression of claudin-2 and claudin-4, meanwhile develop an imbalance of intestinal flora which probably increase serine protease activity, thereby activating the PAR2/ERK signaling and causing the intestinal barrier disorder.
Collapse
Affiliation(s)
- Li Zhao
- Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Peipei Ren
- Affiliated Hospital, Gansu University of Chinese Medicine, Lanzhou, China
| | - Miaolei Wang
- Affiliated Hospital, Gansu University of Chinese Medicine, Lanzhou, China
| | - Jingjing Wang
- Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Xueyun He
- Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Jingyan Gu
- Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Yanyu Lu
- Function Laboratory in College of Basic Medicine, Lanzhou University, Lanzhou, Gansu Province, China
| | - Yana Wu
- Affiliated Hospital, Gansu University of Chinese Medicine, Lanzhou, China
| | - Junhong Liu
- Affiliated Hospital, Gansu University of Chinese Medicine, Lanzhou, China
| | - Longde Wang
- Affiliated Hospital, Gansu University of Chinese Medicine, Lanzhou, China
| | - Hongfang Li
- Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou, China.,Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, China
| |
Collapse
|
|
30
|
Kim SH. [Duodenal Microbiome and Its Clinical Implications in Functional Dyspepsia]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2022; 79:91-98. [PMID: 35342166 DOI: 10.4166/kjg.2022.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/04/2022] [Accepted: 03/15/2022] [Indexed: 11/03/2022]
Abstract
Functional dyspepsia is one of the most common functional gastrointestinal disorders with chronic bothersome epigastric pain or postprandial fullness without a definite organic cause. Despite its high clinical burden, the treatment modalities for modulating impaired motor dysfunction and visceral hypersensitivity have been unsatisfactory. Recently, studies demonstrating low-grade inflammation and dysbiosis of the duodenal mucosa as potential triggers of the disease have attracted attention. Observations, such as an increase in the proportion of oral commensal bacteria in the duodenal mucosa, such as Streptococcus species, highlight the importance of bacterial ecology in developing symptoms of functional dyspepsia. In the near future, anti-inflammatory drugs and probiotics that modulate the host-microbiome interaction are expected to emerge to treat functional dyspepsia.
Collapse
Affiliation(s)
- Sang Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| |
Collapse
|
|
31
|
Aguilera-Lizarraga J, Hussein H, Boeckxstaens GE. Immune activation in irritable bowel syndrome: what is the evidence? Nat Rev Immunol 2022; 22:674-686. [PMID: 35296814 DOI: 10.1038/s41577-022-00700-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2022] [Indexed: 12/15/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that is characterized by abdominal pain and an altered defecation pattern. It affects between 5 and 20% of the general population and can seriously impact quality of life. The pathophysiology of IBS is rather complex and multifactorial including, for example, altered signalling by the gut-brain axis, dysbiosis, abnormal visceral pain signalling and intestinal immune activation. The latter has gained particular interest in recent years, with growing insight into the bidirectional communication between the nervous system and the immune system. In this Review, we detail the current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS and discuss the potential mechanisms involved. Moreover, we describe how immune mediators, particularly those released by mast cells, can directly activate or sensitize pain-transmitting nerves, leading to increased pain signalling and abdominal pain. Finally, we discuss the potential of interventions targeting immune activation as a new therapeutic strategy for patients suffering from IBS.
Collapse
Affiliation(s)
- Javier Aguilera-Lizarraga
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Hind Hussein
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Guy E Boeckxstaens
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
| |
Collapse
|
|
32
|
Varani J, McClintock SD, Aslam MN. Cell-Matrix Interactions Contribute to Barrier Function in Human Colon Organoids. Front Med (Lausanne) 2022; 9:838975. [PMID: 35360746 PMCID: PMC8960989 DOI: 10.3389/fmed.2022.838975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/10/2022] [Indexed: 11/13/2022] Open
Abstract
The importance of cell-matrix adhesion to barrier control in the colon is unclear. The goals of the present study were to: (i) determine if disruption of colon epithelial cell interactions with the extracellular matrix alters permeability control measurement and (ii) determine if increasing the elaboration of protein components of cell-matrix adhesion complexes can mitigate the effects of cell-matrix disruption. Human colon organoids were interrogated for transepithelial electrical resistance (TEER) under control conditions and in the presence of Aquamin®, a multi-mineral product. A function-blocking antibody directed at the C-terminal region of the laminin α chain was used in parallel. The effects of Aquamin® on cell-matrix adhesion protein expression were determined in a proteomic screen and by Western blotting. Aquamin® increased the expression of multiple basement membrane, hemidesmosomal and focal adhesion proteins as well as keratin 8 and 18. TEER values were higher in the presence of Aquamin® than they were under control conditions. The blocking antibody reduced TEER values under both conditions but was most effective in the absence of Aquamin®, where expression of cell-matrix adhesion proteins was lower to begin with. These findings provide evidence that cell-matrix interactions contribute to barrier control in the colon.
Collapse
|
|
33
|
Scuderi SA, Casili G, Lanza M, Ardizzone A, Pantaleo L, Campolo M, Paterniti I, Cucinotta L, Cuzzocrea S, Esposito E. Efficacy of a Product Containing Xyloglucan and Pea Protein on Intestinal Barrier Function in a Partial Restraint Stress Animal Model. Int J Mol Sci 2022; 23:ijms23042269. [PMID: 35216383 PMCID: PMC8875977 DOI: 10.3390/ijms23042269] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/11/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022] Open
Abstract
Functional abdominal bloating and distension (FABD) are common and frequent symptoms in patients with pre-existing gastrointestinal (GI) disorders. FABD is characterized by recurrent abdominal fullness and bloating. The pathophysiology of FABD is still unclear. However, the plausible mechanisms involved are small intestinal bacterial overgrowth (SIBO), imbalance of gut microbiota, visceral hypersensitivity, intestinal permeability alteration, and disruption of intestinal barrier function. Thus, the creation of a barrier on the wall of the intestine could represent an alternative therapeutic strategy to prevent FABD. This study aimed to investigate the effect of two natural substances, Xyloglucan (XG) and Pea-protein (PP), known for their mucosal-protective properties, in an in vivo model of Partial restraint-stress (PRS). Our results showed that the pre-treatment with a product containing XG and PP in stressed-rats was able to reduce the number of abdominal contractions and visceral hypersensitivity. Moreover, XG and PP were able to reduce intestinal permeability alteration, restoring tight-junctions (TJs) expression and decreased the lactulose–mannitol ratio, a quantitative marker used to measure intestinal permeability, compared to PRS-group. In conclusion, the data obtained revealed that the product containing XG and PP was able to restore the normal intestinal-barrier function; therefore, it could be considered a therapeutic strategy to manage FABD.
Collapse
|
|
34
|
Dutta A, Das M. Deciphering the Role of Aquaporins in Metabolic Diseases: A Mini Review. Am J Med Sci 2022; 364:148-162. [DOI: 10.1016/j.amjms.2021.10.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 06/16/2021] [Accepted: 10/21/2021] [Indexed: 12/23/2022]
|
|
35
|
Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases. Biomedicines 2022; 10:biomedicines10020289. [PMID: 35203499 PMCID: PMC8869546 DOI: 10.3390/biomedicines10020289] [Citation(s) in RCA: 111] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 02/04/2023] Open
Abstract
The intestinal mucosal barrier, also referred to as intestinal barrier, is widely recognized as a critical player in gut homeostasis maintenance as it ensures the complex crosstalk between gut microbes (both commensals and pathogens) and the host immune system. Highly specialized epithelial cells constantly cope with several protective and harmful agents to maintain the multiple physiological functions of the barrier as well as its integrity. However, both genetic defects and environmental factors can break such equilibrium, thus promoting gut dysbiosis, dysregulated immune-inflammatory responses, and even the development of chronic pathological conditions. Here, we review and discuss the molecular and cellular pathways underlying intestinal barrier structural and functional homeostasis, focusing on potential alterations that may undermine this fine balance.
Collapse
|
|
36
|
Rastgoo S, Ebrahimi-Daryani N, Agah S, Karimi S, Taher M, Rashidkhani B, Hejazi E, Mohseni F, Ahmadzadeh M, Sadeghi A, Hekmatdoost A. Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management. Front Nutr 2022; 8:746703. [PMID: 34977110 PMCID: PMC8716871 DOI: 10.3389/fnut.2021.746703] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Background and Aims: Although irritable bowel syndrome is one of the most common gastrointestinal disorders presented to gastroenterologists, therapeutic strategies are not yet well-established. Accordingly, we conducted a randomized, double-blind, placebo-controlled, clinical trial to evaluate the possible superiority of adding glutamine supplement to low fermentable oligo- di- monosaccharides and polyols (FODMAP) diet in patients with irritable bowel syndrome (IBS). Methods: Eligible adults were randomized to receive a low FODMAP diet either with glutamine (15 g/day) or a placebo for 6 weeks. The primary endpoint was a significant reduction in IBS-symptom severity score (IBS-SSS). Secondary endpoints were changes in IBS symptoms, stool frequency, consistency, and quality of life. Results: The study group enrolled 50 patients, among which 22 participants from each group completed the study protocol. The glutamine group had significant changes in total IBS-severity score, dissatisfaction of bowel habit and interference with community function (58% reduction; P < 0.001, 57% reduction; P < 0.001, 51% reduction; P = 0.043, respectively). Improvement in IBS-severity score of more than 45% was observed in 22 of 25 participants (88%) in the glutamine group, while it was only 15 of 25 participants (60%) in the control group (p = 0.015). No serious adverse events were observed. Conclusions: Our findings indicated the superiority of adding glutamine supplementation to a low FODMAP diet in amelioration of IBS symptoms while confirming the beneficial effects of a low FODMAP diet in IBS management.
Collapse
Affiliation(s)
- Samira Rastgoo
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi-Daryani
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Sara Karimi
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Taher
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahram Rashidkhani
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Hejazi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mohseni
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mina Ahmadzadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
37
|
OUP accepted manuscript. Pathog Dis 2022; 80:6521441. [DOI: 10.1093/femspd/ftac003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/30/2021] [Accepted: 02/01/2022] [Indexed: 11/15/2022] Open
|
|
38
|
Mechanism of QingHuaZhiXie Prescription Regulating TLR4-IECs Pathway in the Intervention of Diarrhea Predominant Irritable Bowel Syndrome. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5792130. [PMID: 34795785 PMCID: PMC8594983 DOI: 10.1155/2021/5792130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 09/25/2021] [Accepted: 10/25/2021] [Indexed: 12/30/2022]
Abstract
To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.
Collapse
|
|
39
|
Grover M, Berumen A, Peters S, Wei T, Breen-Lyles M, Harmsen WS, Busciglio I, Burton D, Vazquez Roque M, DeVault KR, Camilleri M, Wallace M, Dasari S, Neumann H, Houghton LA. Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression. Aliment Pharmacol Ther 2021; 54:1179-1192. [PMID: 34472640 DOI: 10.1111/apt.16591] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/26/2021] [Accepted: 08/17/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. AIM To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. RESULTS Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = -0.48, FDR = 0.01) and pain (r = -0.41, FDR = 0.02) thresholds. CONCLUSION Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS.
Collapse
Affiliation(s)
- Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Antonio Berumen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephanie Peters
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ting Wei
- Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Margaret Breen-Lyles
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Irene Busciglio
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Duane Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Maria Vazquez Roque
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Kenneth R DeVault
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Surendra Dasari
- Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Helmut Neumann
- Department of Medicine I, University Medical Center Mainz, Mainz, Germany.,GastroZentrum Lippe, Bad Salzuflen, Germany
| | - Lesley A Houghton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| |
Collapse
|
|
40
|
Ray P, Pandey U, Das D, Aich P. Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice. Dig Dis Sci 2021; 66:3776-3791. [PMID: 33386517 DOI: 10.1007/s10620-020-06729-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 11/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The consequence of treatment with antibiotics on the gut microbiota can be destructive. The antibiotics, however, can be utilized to understand the role of gut microbiota on the host physiology. AIM Earlier, we reported the efficacy of vancomycin in gut microbiota perturbation. We continued to understand the effect of restoration kinetics of perturbed gut microbiota on the immunity and behavior of Th1 (C57BL/6)- and Th2 (BALB/c)-biased mice. METHODS We studied restoration kinetics of the gut microbiota for two months following the withdrawal of vancomycin treatment in both mice strains. We analyzed cecal microbiome composition, different behavioral assays, and expression of select genes associated with stress and barrier function in gut and brain. RESULTS Metagenomic analysis of gut microbiota revealed that the treatment with vancomycin caused a significant decrease in the relative abundance of Firmicutes and Bacteroidetes phyla with a time-dependent increase in Proteobacteria and Verrucomicrobia phyla. Maximum restoration (> 70%) of gut microbiota happened by the 15th day of withdrawal of vancomycin. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. We established the correlation patterns of gut microbiota alteration and its effect on (a) the behavior of mice, (b) expression of key brain molecules, and (c) immunity-related genes. CONCLUSIONS The results revealed that the gut microbiome profiling, behavior, and immune responses varied significantly between Th1- and Th2-biased mice. By withdrawing the treatment with vancomycin of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal (untreated control) level.
Collapse
Affiliation(s)
- Pratikshya Ray
- School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. - Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India
| | - Uday Pandey
- School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. - Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India
| | - Debasmita Das
- School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. - Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India
| | - Palok Aich
- School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. - Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India.
| |
Collapse
|
|
41
|
Benjak Horvat I, Gobin I, Kresović A, Hauser G. How can probiotic improve irritable bowel syndrome symptoms? World J Gastrointest Surg 2021; 13:923-940. [PMID: 34621470 PMCID: PMC8462084 DOI: 10.4240/wjgs.v13.i9.923] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/22/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
The onset and manifestations of irritable bowel syndrome (IBS) is associated with several factors, and the pathophysiology involves various central and peripheral mechanisms. Most studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with IBS. Numerous clinical trials have assessed the efficacy of probiotics for IBS with controversial conclusions. Several clinical trials have suggested that probiotics can improve global IBS symptoms, while others only improve individual IBS symptoms, such as bloating scores and abdominal pain scores. Only a few clinical trials have found no apparent effect of probiotics on IBS symptoms. Generally, probiotics appear to be safe for patients with IBS. However, the question of which probiotics should be used for certain IBS subtypes remains unresolved. In everyday practice, the dose of the recommended probiotic remains questionable, as well as how long the probiotic should be used in therapy. The use of probiotics in the M subtype and non-classified IBS is particularly problematic, in which combination therapy should be recommended due to the change in symptoms. Therefore, new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.
Collapse
Affiliation(s)
- Indira Benjak Horvat
- Department of Gastroenterology, Varaždin General Hospital, Varažin 42000, Croatia
| | - Ivana Gobin
- Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Andrea Kresović
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Faculty of Medicine, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka 51000, Croatia
| |
Collapse
|
|
42
|
Pérez de Arce E, Quera R, Quigley EMM. The Dilemma of Persistent Irritable Bowel Syndrome Symptoms in Patients with Quiescent Inflammatory Bowel Disease. Gastroenterol Clin North Am 2021; 50:689-711. [PMID: 34304795 DOI: 10.1016/j.gtc.2021.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome and inflammatory bowel disease differ in their natural evolution, etiopathogenesis, diagnostic criteria, and therapeutic approach. However, recent evidence has suggested some similarities in mechanisms underlying symptom development and progression. There is a relevant role for alterations in the microbiome-brain-gut axis in both diseases. The presence of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is common in clinical practice. To determine the cause of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is a clinical challenge. This review aims to illustrate possible causes and solutions for these patients.
Collapse
Affiliation(s)
- Edith Pérez de Arce
- Department of Medicine, Division of Gastroenterology, Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar 999, Independencia, Región Metropolitana, Santiago, Chile
| | - Rodrigo Quera
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Universidad de los Andes, Estoril 450, Las Condes, Región Metropolitana, Santiago, Chile
| | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, TX, USA.
| |
Collapse
|
|
43
|
Peters S, Pascoe B, Wu Z, Bayliss SC, Zeng X, Edwinson A, Veerabadhran-Gurunathan S, Jawahir S, Calland JK, Mourkas E, Patel R, Wiens T, Decuir M, Boxrud D, Smith K, Parker CT, Farrugia G, Zhang Q, Sheppard SK, Grover M. Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans. Commun Biol 2021; 4:1015. [PMID: 34462533 PMCID: PMC8405632 DOI: 10.1038/s42003-021-02554-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 08/13/2021] [Indexed: 02/08/2023] Open
Abstract
Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some C. jejuni strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized. We combined pangenome-wide association studies and phenotypic assays to compare C. jejuni isolates from patients who developed PI-IBS with those who did not. We show that variation in bacterial stress response (Cj0145_phoX), adhesion protein (Cj0628_CapA), and core biosynthetic pathway genes (biotin: Cj0308_bioD; purine: Cj0514_purQ; isoprenoid: Cj0894c_ispH) were associated with PI-IBS development. In vitro assays demonstrated greater adhesion, invasion, IL-8 and TNFα secretion on colonocytes with PI-IBS compared to PI-no-IBS strains. A risk-score for PI-IBS development was generated using 22 genomic markers, four of which were from Cj1631c, a putative heme oxidase gene linked to virulence. Our finding that specific Campylobacter genotypes confer greater in vitro virulence and increased risk of PI-IBS has potential to improve understanding of the complex host-pathogen interactions underlying this condition. Stephanie Peters, Ben Pascoe, et al. use whole-genome sequencing and phenotypic analysis of clinical strains from patients to identify potential genetic factors involved in irritable bowel syndrome resulting from Campylobacter jejuni infection. Their data suggest that genes involved in the bacterial stress response and biosynthetic pathways may contribute toward irritable bowel syndrome, providing further insight into links between Campylobacter genotypes and risk of disease.
Collapse
Affiliation(s)
- Stephanie Peters
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Ben Pascoe
- The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
| | - Zuowei Wu
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
| | - Sion C Bayliss
- The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
| | - Ximin Zeng
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Adam Edwinson
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Jessica K Calland
- The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
| | - Evangelos Mourkas
- The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
| | - Robin Patel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Terra Wiens
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Marijke Decuir
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - David Boxrud
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Kirk Smith
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Craig T Parker
- United States Department of Agriculture, Albany, CA, USA
| | - Gianrico Farrugia
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Qijing Zhang
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
| | - Samuel K Sheppard
- The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK.
| | - Madhusudan Grover
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
| |
Collapse
|
|
44
|
Leech B, McIntyre E, Steel A, Sibbritt D. Health-seeking behaviour, views and preferences of adults with suspected increased intestinal permeability: A cross-sectional survey of Australian adults. Integr Med Res 2021; 11:100757. [PMID: 34401323 PMCID: PMC8358409 DOI: 10.1016/j.imr.2021.100757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 06/14/2021] [Accepted: 07/02/2021] [Indexed: 12/11/2022] Open
Abstract
Background The public health consequence of increased intestinal permeability (IP) is currently limited by the lack of patient-centred research. This study aims to describe the health-seeking behaviour of Australian adults with suspected IP. Methods A cross-sectional survey of 589 Australian adults who have been diagnosed with IP or have suspected (undiagnosed) IP. Results The majority (56.2%) of participants with suspected IP reported self-diagnosing their condition, with the majority (56.7%) of these participants preferring to be assessed using an accurate method by a general practitioner or naturopath. On average, Australian adults with suspected IP spent 11.1 (95% CI: 9.5, 12.8) years between first suspecting IP and receiving a formal diagnosis. Over the previous 12 months, participants spent an average of $699 on consultation fees, $2176 on dietary supplements for the treatment of IP, and an average of $287 on the assessment of IP. Furthermore, participants who find it difficult to live on their available household income spent significantly more (mean=$2963) on dietary supplements compared to participants who find it easy to live on their available household income ($1918) (p=0.015). Conclusion The investigation of Australian adults with suspected IP found the majority of participants experienced a considerable length of time between first suspecting IP and receiving a diagnosis of IP. The out-of-pocket expenditure associated with the management of IP suggests a financial burden for people with suspected IP. The results of this study provide novel patient-centred considerations that can be used to inform a clinical practice guideline for the management of IP.
Collapse
Affiliation(s)
- Bradley Leech
- Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, Australia
| | - Erica McIntyre
- Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, Australia
| | - Amie Steel
- Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, Australia
| | - David Sibbritt
- Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, Australia
| |
Collapse
|
|
45
|
Lee KJ. The Usefulness of Symptom-based Subtypes of Functional Dyspepsia for Predicting Underlying Pathophysiologic Mechanisms and Choosing Appropriate Therapeutic Agents. J Neurogastroenterol Motil 2021; 27:326-336. [PMID: 34210898 PMCID: PMC8266502 DOI: 10.5056/jnm21042] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/01/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Functional dyspepsia (FD) is considered to be a heterogeneous disorder with different pathophysiological mechanisms or pathogenetic factors. In addition to traditional mechanisms, novel concepts regarding pathophysiologic mechanisms of FD have been proposed. Candidates of therapeutic agents based on novel concepts have also been suggested. FD is a symptom complex and currently diagnosed by symptom-based Rome criteria. In the Rome criteria, symptom-based subtypes of FD including postprandial distress syndrome and epigastric pain syndrome are recommended to be used, based on the assumption that each subtype is more homogenous in terms of underlying pathophysiologic mechanisms than FD as a whole. In this review, the usefulness of symptombased subtypes of FD for predicting underlying pathophysiologic mechanisms and choosing appropriate therapeutic agents was evaluated. Although several classic pathophysiologic mechanisms are suggested to be associated with individual dyspeptic symptoms, symptom-based subtypes of FD are not specific for a certain pathogenetic factor or pathophysiologic mechanism, and may be frequently associated with multiple pathophysiologic abnormalities. Novel concepts on the pathophysiology of FD show complex interactions between pathophysiologic mechanisms and pathogenetic factors, and prediction of underlying mechanisms of individual patients simply by the symptom pattern or symptom-based subtypes may not be accurate in a considerable proportion of cases. Therefore, subtyping by the Rome criteria appears to have limited value to guide therapeutic strategy, suggesting that the addition of objective parameters or subclassification reflecting physiologic or pathologic tests may be necessary for the targeted therapeutic approaches, particularly when therapeutic agents targeting novel mechanisms are available.
Collapse
Affiliation(s)
- Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
| |
Collapse
|
|
46
|
Elbadawi M, Ammar RM, Aziz-Kalbhenn H, Rabini S, Klauck SM, Dawood M, Saeed MEM, Kampf CJ, Efferth T. Anti-inflammatory and tight junction protective activity of the herbal preparation STW 5-II on mouse intestinal organoids. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 88:153589. [PMID: 34111617 DOI: 10.1016/j.phymed.2021.153589] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/17/2021] [Accepted: 04/29/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a functional bowel disorder, in which recurrent abdominal pain is associated with defecation or a change in bowel habits. STW 5-II is a combination of six medicinal herbs with a clinically proven efficacy in managing IBS. AIM This study aims to establish an in vitro IBS model using mouse intestinal organoids and to explore the anti-inflammatory and tight junction protective activities of the multi-herbal preparation STW 5-II. METHODS Intestinal organoids were cultured in 1:1 Matrigel™ and medium domes. Inflammation and tight junction disruption were induced by a cocktail of cytokines (TNFα, IFNγ, IL-1β, IL-6) and bacterial proteins (LPS, flagellin). Organoids were treated with different concentrations of STW 5-II, and its multi-target activity was assessed using microarray analyses, RT-qPCR, immunofluorescence, western blot, immunohistochemistry, and a FITC permeability assay. In addition, we analyzed the expression of pNF-κB, pSTAT1, iNOS and ZO-1. In silico analyses were conducted to predict and identify the active components that may be responsible in mediating the multi-target anti-inflammatory activity of STW 5-II. RESULTS An organoid based IBS model was successfully established. STW 5-II effectively reduced the cytokines-induced overexpression of the pro-inflammatory mediators pNF-κB, pSTAT1 and iNOS. Moreover, STW 5-II attenuated cytokine-mediated downregulation of the tight junction protein, ZO-1. This finding was confirmed by a FITC permeability assay. In silico analyses revealed a promising inhibitory activity of some isolated compounds from STW 5-II against NF-κB, STAT1 and iNOS. CONCLUSION STW 5-II possesses multiple anti-inflammatory as well as tight junction protective activities that could explain its clinically proven efficacy in managing IBS symptoms.
Collapse
Affiliation(s)
- Mohamed Elbadawi
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Ramy M Ammar
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Heba Aziz-Kalbhenn
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Sabine Rabini
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Sabine M Klauck
- Division of Cancer Genome Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Mona Dawood
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany; Department of Molecular Biology, Faculty of Medical Laboratory Science, Al-Neelain University, Khartoum, Sudan
| | - Mohamed E M Saeed
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | | | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
| |
Collapse
|
|
47
|
Naseri K, Dabiri H, Rostami-Nejad M, Yadegar A, Houri H, Olfatifar M, Sadeghi A, Saadati S, Ciacci C, Iovino P, Zali MR. Influence of low FODMAP-gluten free diet on gut microbiota alterations and symptom severity in Iranian patients with irritable bowel syndrome. BMC Gastroenterol 2021. [PMID: 34261437 DOI: 10.1186/s12876-021-01868-5.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Recently, dietary restriction of fermentable carbohydrates (a low-FODMAP diet) in combination with a gluten-free diet (GFD) has been proposed to reduce the symptoms in irritable bowel syndrome (IBS) patients. Different studies reported that IBS has been associated with dysbiosis in the gut microbiota. Additionally, a few studies have reported inflammation in the gastrointestinal (GI) system of adults with IBS. In this study, we aimed to investigate the effects of low FODMAP-gluten free diet (LF-GFD) on clinical symptoms, intestinal microbiota diversity, and fecal calprotectin (FC) level in Iranian patients with IBS. DESIGN In this clinical trial study, 42 patients with IBS (Rome IV criteria) underwent LF-GFD intervention for 6 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS), and fecal samples were collected at baseline and after intervention and analyzed by quantitative 16 S rRNA PCR assay. The diversity of gut microbiota compared before and after 6 weeks of dietary intervention. FC was also analyzed by the ELISA method. RESULTS Thirty patients (mean age 37.8 ± 10.7 years) completed the 6-week diet. The IBS-SSS was significantly (P = 0.001) reduced after LF-GFD intervention compared to the baseline. Significant microbial differences before and after intervention were noticed in fecal samples. A significant increase was found in Bacteroidetes, and the Firmicutes to Bacteroidetes (F/B) ratio was significantly (P = 0.001) decreased after the dietary intervention. The value of FC was significantly decreased after 6 weeks of dietary intervention (P = 0.001). CONCLUSIONS Our study suggests that patients with IBS under an LF-GFD had a significant improvement in IBS symptoms severity, with reduced FC level following normalization of their gut microbiota composition. Further rigorous trials are needed to establish a long-term efficacy and safety of this dietary intervention for personalized nutrition in IBS. Clinical Trial Registry Number: IRCT20100524004010N26.
Collapse
Affiliation(s)
- Kaveh Naseri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., Velenjak, Tehran, Iran.
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., Velenjak, Tehran, Iran
| | - Meysam Olfatifar
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeede Saadati
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Carolina Ciacci
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, Università di Salerno, Via Allende, 84081, Salerno, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, Università di Salerno, Via Allende, 84081, Salerno, Italy
| | - Mohammad Reza Zali
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
48
|
Naseri K, Dabiri H, Rostami-Nejad M, Yadegar A, Houri H, Olfatifar M, Sadeghi A, Saadati S, Ciacci C, Iovino P, Zali MR. Influence of low FODMAP-gluten free diet on gut microbiota alterations and symptom severity in Iranian patients with irritable bowel syndrome. BMC Gastroenterol 2021; 21:292. [PMID: 34261437 PMCID: PMC8278734 DOI: 10.1186/s12876-021-01868-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 06/21/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Recently, dietary restriction of fermentable carbohydrates (a low-FODMAP diet) in combination with a gluten-free diet (GFD) has been proposed to reduce the symptoms in irritable bowel syndrome (IBS) patients. Different studies reported that IBS has been associated with dysbiosis in the gut microbiota. Additionally, a few studies have reported inflammation in the gastrointestinal (GI) system of adults with IBS. In this study, we aimed to investigate the effects of low FODMAP-gluten free diet (LF-GFD) on clinical symptoms, intestinal microbiota diversity, and fecal calprotectin (FC) level in Iranian patients with IBS. DESIGN In this clinical trial study, 42 patients with IBS (Rome IV criteria) underwent LF-GFD intervention for 6 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS), and fecal samples were collected at baseline and after intervention and analyzed by quantitative 16 S rRNA PCR assay. The diversity of gut microbiota compared before and after 6 weeks of dietary intervention. FC was also analyzed by the ELISA method. RESULTS Thirty patients (mean age 37.8 ± 10.7 years) completed the 6-week diet. The IBS-SSS was significantly (P = 0.001) reduced after LF-GFD intervention compared to the baseline. Significant microbial differences before and after intervention were noticed in fecal samples. A significant increase was found in Bacteroidetes, and the Firmicutes to Bacteroidetes (F/B) ratio was significantly (P = 0.001) decreased after the dietary intervention. The value of FC was significantly decreased after 6 weeks of dietary intervention (P = 0.001). CONCLUSIONS Our study suggests that patients with IBS under an LF-GFD had a significant improvement in IBS symptoms severity, with reduced FC level following normalization of their gut microbiota composition. Further rigorous trials are needed to establish a long-term efficacy and safety of this dietary intervention for personalized nutrition in IBS. Clinical Trial Registry Number: IRCT20100524004010N26.
Collapse
Affiliation(s)
- Kaveh Naseri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., Velenjak, Tehran, Iran.
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., Velenjak, Tehran, Iran
| | - Meysam Olfatifar
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeede Saadati
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Carolina Ciacci
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, Università di Salerno, Via Allende, 84081, Salerno, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, Università di Salerno, Via Allende, 84081, Salerno, Italy
| | - Mohammad Reza Zali
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
49
|
Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, Agrawal A, Aziz I, Farmer AD, Eugenicos MP, Moss-Morris R, Yiannakou Y, Ford AC. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021; 70:1214-1240. [PMID: 33903147 DOI: 10.1136/gutjnl-2021-324598] [Citation(s) in RCA: 254] [Impact Index Per Article: 63.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/30/2021] [Accepted: 04/06/2021] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
Collapse
Affiliation(s)
- Dipesh H Vasant
- Neurogastroenterology Unit, Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.,Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
| | - Peter A Paine
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK.,Gastroenterology, Salford Royal Foundation Trust, Salford, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.,Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Hazel A Everitt
- Primary Care and Population Sciences, University of Southampton, Southampton, UK
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
| | - Anurag Agrawal
- Gastroenterology, Doncaster and Bassetlaw Hospitals NHS Trust, Armthorpe Road, Doncaster, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Adam D Farmer
- Department of Gastroenterology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.,School of Medicine, Keele University, Keele, UK
| | - Maria P Eugenicos
- Department of Gastroenterology, University of Edinburgh, Western General Hospital, Edinburgh, UK
| | - Rona Moss-Morris
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Yan Yiannakou
- Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK .,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| |
Collapse
|
|
50
|
Abstract
Epidemiologic data support that acute gastrointestinal infection is one of the strongest risk factors for development of irritable bowel syndrome (IBS). Risk of post-infection IBS (PI-IBS) seems to be greater with bacterial and protozoal than viral enterocolitis. Younger individuals, women, and those with severe enterocolitis are more likely to develop PI-IBS. Disease mechanisms in animal models and humans involve chronic perturbation of intestinal microbiome, epithelial and neuronal remodeling, and immune activation. These mechanisms can lead to luminal (increased proteolytic activity, altered bile acid composition) and physiologic (increased permeability, transit changes, and visceral hypersensitivity) alterations that can mediate PI-IBS symptoms.
Collapse
Affiliation(s)
- Antonio Berumen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Adam L Edwinson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Medicine and Physiology, Enteric NeuroScience Program, 200 First Street Southwest, Rochester, MN 55905, USA.
| |
Collapse
|