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Zeraattalab-Motlagh S, Ranjbar M, Mohammadi H, Adibi P. Nutritional Interventions in Adult Patients With Irritable Bowel Syndrome: An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Clinical Trials. Nutr Rev 2025; 83:e1343-e1354. [PMID: 39110917 DOI: 10.1093/nutrit/nuae107] [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] [Indexed: 02/14/2025] Open
Abstract
CONTEXT There is still debate regarding the effect of nutritional interventions in improving irritable bowel syndrome (IBS) symptoms. OBJECTIVES The aim was to examine the evidence certainty and validity of all existing meta-analyses of intervention trials on nutritional interventions in patients with IBS. DATA SOURCES Scopus, PubMed, and Web of Science were reviewed until June 2023. DATA EXTRACTION Meta-analyses assessing the impacts of nutritional interventions in adults with IBS were entered. Effect sizes of nutritional interventions were recalculated by applying a random-effects model. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) was implemented to determine evidence certainty. RESULTS A total of 175 trials in 58 meta-analyses were entered describing the effects of 11 nutritional interventions on IBS-related outcomes. Nutritional interventions had beneficial effects on some IBS-related outcomes. For instance, soluble fiber, peppermint oil, and aloe vera improved IBS symptoms, and vitamin D3 and curcumin improved IBS symptom severity. Tongxieyaofang improved abdominal pain severity and stool frequency. Nevertheless, these outcomes have mainly shown small effects and low to very low evidence certainty. With regard to abdominal pain after probiotic supplementation (relative risk [RR]: 4.04; 95% confidence interval [CI]: 2.36, 6.92; GRADE = moderate) and IBS symptoms after a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (RR: 1.48; 95% CI: 1.14, 1.93; GRADE = moderate), there was evidence that probiotics and a low-FODMAP diet can confer clinical and favorable effects. CONCLUSION The current review does not support nutritional interventions for improving IBS symptoms. With regard to probiotics and a low-FODMAP diet, considering limitations like short-term study duration, there was an influential clinical impact. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023429991.
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Affiliation(s)
| | - Mahsa Ranjbar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 1417613151, Iran
| | - Hamed Mohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 1417613151, Iran
| | - Peyman Adibi
- Isfahan Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
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Capirchio L, Rousseaux C, Dubuquoy C, Ouwehand AC, Maquet V, Modica S, Louis E, Desreumaux P, Tack J. A Synbiotic Combining Chitin-Glucan and Lactobacillus acidophilus NCFM Induces a Colonic Molecular Signature Soothing Intestinal Pain and Inflammation in an Animal Model of IBS. Int J Mol Sci 2024; 25:10732. [PMID: 39409061 PMCID: PMC11476380 DOI: 10.3390/ijms251910732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
Chitin-glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1β, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes.
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Affiliation(s)
- Lena Capirchio
- Hepato-Gastroenterology Department, Centre Hospitalier Wallonie-Picarde, 7500 Tournai, Belgium;
| | | | | | | | - Véronique Maquet
- KitoZyme SA, Parc Industriel des Hauts Sarts Zone 2, Rue de Milmort 680, 4040 Herstal, Belgium; (V.M.); (S.M.)
| | - Salvatore Modica
- KitoZyme SA, Parc Industriel des Hauts Sarts Zone 2, Rue de Milmort 680, 4040 Herstal, Belgium; (V.M.); (S.M.)
| | - Edouard Louis
- Department of Gastroenterology, Centre Hospitalier Universitaire de Liège, 4000 Liège, Belgium;
| | - Pierre Desreumaux
- U1286—INFINITE—Institute for Translational Research in Inflammation, University Lille, Inserm, CHU Lille, 59000 Lille, France
- Hepato-Gastroenterology Department, Lille University Hospital, 59000 Lille, France
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium;
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
- Rome Foundation, Raleigh, NC 27614, USA
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Nekrasov E, Vita AA, Bradley R, Contractor N, Gunaratne NM, Kuehn M, Kitisin R, Patel D, Woods E, Zhou B. Changes in Digestive Health, Satiety and Overall Well-Being after 14 Days of a Multi-Functional GI Primer Supplement. Nutrients 2024; 16:3173. [PMID: 39339773 PMCID: PMC11434699 DOI: 10.3390/nu16183173] [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: 08/09/2024] [Revised: 09/04/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
A recent review proposed a role for multi-functional food or supplement products in priming the gut to support both digestive and systemic health. Accordingly, we designed and eva-luated the effect of a multi-functional gastrointestinal (GI) primer supplement on participant-reported measures for digestive health, quality-of-life (e.g., energy/vitality and general health), and reasons for satiation (e.g., attitudes towards food and eating). In this single-arm clinical trial, 68 participants with mild digestive symptoms consumed the GI primer supplement daily for 14 days. Digestive symptoms were evaluated daily from baseline (Day 0) through Day 14. At baseline and Day 14, participants reported their stool consistency, reasons for satiation, and quality-of-life measures using validated questionnaires. At Day 14, participants reported significant improvements in all (13/13) digestive symptom parameters (p-values < 0.05) and an increase in % of stools with normal consistencies. There were significant improvements (p-values < 0.05) in energy/vitality and general health, and in specific attitudes towards food and eating (e.g., physical satisfaction, planned amount, decreased eating priority, decreased food appeal, and self-consciousness). Results suggest the GI primer supplement promotes digestive health, improves quality of life, and impacts attitudes towards food/eating. This study provides preliminary support for the gut priming hypothesis through which multi-functional digestive products may improve GI health.
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Affiliation(s)
| | - Alexandra Adorno Vita
- Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
| | - Ryan Bradley
- Amway Innovation and Science, Buena Park, CA 90621, USA
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, La Jolla, CA 92093, USA
| | | | | | - Marissa Kuehn
- Amway Innovation and Science, Buena Park, CA 90621, USA
| | - Rick Kitisin
- Amway Innovation and Science, Buena Park, CA 90621, USA
| | - Deval Patel
- Amway Innovation and Science, Ada, MI 49355, USA
| | - Erin Woods
- Amway Innovation and Science, Buena Park, CA 90621, USA
| | - Bo Zhou
- Amway Innovation and Science, Buena Park, CA 90621, USA
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Li F, Yano Y, Étiévant L, Daniel CR, Sharma SV, Brown EL, Li R, Loftfield E, Lan Q, Sinha R, Moshiree B, Inoue-Choi M, Vogtmann E. The Time-Dependent Association Between Irritable Bowel Syndrome and All-Cause and Cause-Specific Mortality: A Prospective Cohort Study Within the UK Biobank. Am J Gastroenterol 2024; 119:1373-1382. [PMID: 38275237 PMCID: PMC11222041 DOI: 10.14309/ajg.0000000000002675] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 12/20/2023] [Indexed: 01/27/2024]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank. METHODS We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 years). RESULTS A total of 25,697 participants (5.1%) had a history of IBS at baseline. After a median follow-up of 13.7 years, a total of 44,499 deaths occurred. Having an IBS diagnosis was strongly associated with lower risks of all-cause (HR = 0.70, 95% CI = 0.62-0.78) and all-cancer (HR = 0.69, 95% CI = 0.60-0.79) mortality in the first 5 years of follow-up. These associations were attenuated over follow-up, but even after 10 years of follow-up, associations remained inverse (all-cause: HR = 0.89, 95% CI = 0.84-0.96; all-cancer: HR = 0.87, 95% CI = 0.78-0.97) after full adjustment. Individuals with IBS had decreased risk of mortality from breast, prostate, and colorectal cancers in some of the follow-up time categories. DISCUSSION We found that earlier during follow-up, having diagnosed IBS was associated with lower mortality risk, and the association attenuated over time. Additional studies to understand whether specific factors, such as lifestyle and healthcare access, explain the inverse association between IBS and mortality are needed.
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Affiliation(s)
- Fangyu Li
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Yukiko Yano
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Lola Étiévant
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Carrie R. Daniel
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA
| | - Shreela V. Sharma
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston; Houston, TX, USA
| | - Eric L. Brown
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston; Houston, TX, USA
| | - Ruosha Li
- Department of Biostatistics and Data Science, School of Public Health, University of Texas Health Science Center at Houston; Houston, TX, USA
| | - Erikka Loftfield
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Qing Lan
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Rashmi Sinha
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Baharak Moshiree
- Division of Gastroenterology, Hepatology, and Nutrition, Atrium Health, Wake Forest University, Charlotte, North Carolina; Charlotte, NC, USA
| | - Maki Inoue-Choi
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
| | - Emily Vogtmann
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Bethesda, MD, USA
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Ford AC, Staudacher HM, Talley NJ. Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target. Gut 2024; 73:1199-1211. [PMID: 38697774 DOI: 10.1136/gutjnl-2023-331833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/23/2024] [Indexed: 05/05/2024]
Abstract
Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.
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Affiliation(s)
- Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
| | - Heidi M Staudacher
- Deakin University-Geelong Waterfront Campus, Geelong, Victoria, Australia
| | - Nicholas J Talley
- Health, University of Newcastle, Callaghan, New South Wales, Australia
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Ishioh M, Nozu T, Miyagishi S, Igarashi S, Funayama T, Ueno N, Okumura T. Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats. Biochem Pharmacol 2024; 224:116201. [PMID: 38608783 DOI: 10.1016/j.bcp.2024.116201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/20/2024] [Accepted: 04/09/2024] [Indexed: 04/14/2024]
Abstract
Intestinal barrier dysfunction, leaky gut, is implicated in various diseases, including irritable bowel syndrome (IBS) and neurodegenerative conditions like Alzheimer's disease. Our recent investigation revealed that basal forebrain cholinergic neurons (BFCNs), critical for cognitive function, receive signals from butyrate and orexin, playing a role in regulating intestinal barrier function through adenosine A2B signaling and the vagus. This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorpheniramine, an histamine H1 receptor antagonist, not ranitidine, an H2 receptor antagonist. The SKF91488-induced improvement in colonic hyperpermeability was blocked by vagotomy, intracisternal pirenzepine (suppressing BFCNs activity), or alloxazine (an adenosine A2B receptor antagonist). Additionally, intracisternal chlorpheniramine injection eliminated butyrate-induced improvement in colonic hyperpermeability. These findings suggest that brain histamine, acting via the histamine H1 receptor, regulates intestinal barrier function involving BFCNs, adenosine A2B signaling, and the vagus. Brain histamine appears to centrally regulate intestinal barrier function influenced by butyrate, differentiating its actions from peripheral histamine in conditions like IBS, where mast cell-derived histamine induces leaky gut. Brain histamine emerges as a potential pharmacological target for diseases associated with leaky gut, such as dementia and IBS.
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Affiliation(s)
- Masatomo Ishioh
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan.
| | - Tsukasa Nozu
- Department of General Medicine, Asahikawa Medical University, Japan; Department of Regional Medicine and Education, Asahikawa Medical University, Japan; Center for Medical Education, Asahikawa Medical University, Japan
| | - Saori Miyagishi
- Department of General Medicine, Asahikawa Medical University, Japan
| | - Sho Igarashi
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Takuya Funayama
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Nobuhiro Ueno
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan
| | - Toshikatsu Okumura
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan
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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.
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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
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Sjölund J, Kull I, Bergström A, Ljótsson B, Törnblom H, Olén O, Simrén M. Quality of Life and Bidirectional Gut-Brain Interactions in Irritable Bowel Syndrome From Adolescence to Adulthood. Clin Gastroenterol Hepatol 2024; 22:858-866.e6. [PMID: 37802270 DOI: 10.1016/j.cgh.2023.09.022] [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: 06/16/2023] [Revised: 09/07/2023] [Accepted: 09/18/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUNDS AND AIMS Reports on cross-sectional and longitudinal associations between health-related quality of life (HRQoL), psychological distress, and irritable bowel syndrome (IBS) in the adolescent and young adult general population are few. We aimed to describe cross-sectional associations between HRQoL and IBS in adolescence and young adulthood, and examine bidirectional gut-brain interactions in the transition from childhood to adulthood. METHODS We included 3391 subjects from a prospective birth cohort study, with data on IBS at 16 years of age and 24 years of age. IBS was assessed using the pediatric Rome III (16 years of age) and the adult Rome IV (24 years of age) diagnostic questionnaires. HRQoL and psychological distress were assessed through EQ-5D. Sex-adjusted logistic regression models were used to examine associations between overall HRQoL/psychological distress at 16 years of age and new-onset IBS at 24 years of age (brain-gut) and between IBS at 16 years of age and new-onset psychological distress at 24 years of age (gut-brain). RESULTS In subjects with vs without IBS at 16 and 24 years of age, overall HRQoL (EQ visual analog scale, EQ-5D index value) was lower, and it was more common reporting problems in 4 of 5 EQ-5D dimensions (all P < .05). EQ-5D index value at 16 years of age was inversely associated (odds ratio [OR], 0.1, 95% confidence interval [CI], 0.01-0.6), and psychological distress at 16 years of age was positively associated (OR, 1.6; 95% CI, 1.2-2.3), with new-onset IBS at 24 years of age. Having any abdominal pain-related disorder of gut-brain interaction at 16 years of age was associated with new-onset psychological distress at 24 years of age (OR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS Adolescents and young adults with IBS in the general population have impaired HRQoL. Bidirectional gut-brain interactions are relevant for symptom generation in abdominal pain-related disorders of gut-brain interaction, and for HRQoL impairment and psychological distress in the transition from childhood to adulthood.
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Affiliation(s)
- Jessica Sjölund
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
| | - Inger Kull
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Research Unit, Sachs' Children's Hospital, Stockholm, Sweden
| | - Anna Bergström
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden
| | - Brjánn Ljótsson
- Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ola Olén
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Unit of Pediatric Gastroenterology and Nutrition, Sachs' Children's Hospital, Stockholm, Sweden; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - 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, Chapel Hill, North Carolina
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9
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Ford AC. Ebastine for the treatment of irritable bowel syndrome: old drug, new tricks? Gut 2024; 73:393-394. [PMID: 38302258 DOI: 10.1136/gutjnl-2024-331927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 01/19/2024] [Indexed: 02/03/2024]
Affiliation(s)
- 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
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10
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Goodoory VC, Tuteja AK, Black CJ, Ford AC. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol 2024; 22:243-251.e5. [PMID: 36858143 DOI: 10.1016/j.cgh.2023.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 02/02/2023] [Accepted: 02/13/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND & AIMS Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS. METHODS We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials. CONCLUSIONS Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.
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Affiliation(s)
- Vivek C Goodoory
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Ashok K Tuteja
- Division of Gastroenterology, Hepatology & Nutrition, University of Utah, Salt Lake City, Utah; George E. Wahlen V.A. Medical Center, Salt Lake City, Utah
| | - Christopher J Black
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.
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11
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Shen X, Xie A, Li Z, Jiang C, Wu J, Li M, Yue X. Research Progress for Probiotics Regulating Intestinal Flora to Improve Functional Dyspepsia: A Review. Foods 2024; 13:151. [PMID: 38201179 PMCID: PMC10778471 DOI: 10.3390/foods13010151] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/05/2023] [Accepted: 12/08/2023] [Indexed: 01/12/2024] Open
Abstract
Functional dyspepsia (FD) is a common functional gastrointestinal disorder. The pathophysiology remains poorly understood; however, alterations in the small intestinal microbiome have been observed. Current treatments for FD with drugs are limited, and there are certain safety problems. A class of active probiotic bacteria can control gastrointestinal homeostasis, nutritional digestion and absorption, and the energy balance when taken in certain dosages. Probiotics play many roles in maintaining intestinal microecological balance, improving the intestinal barrier function, and regulating the immune response. The presence and composition of intestinal microorganisms play a vital role in the onset and progression of FD and serve as a critical factor for both regulation and potential intervention regarding the management of this condition. Thus, there are potential advantages to alleviating FD by regulating the intestinal flora using probiotics, targeting intestinal microorganisms. This review summarizes the research progress of probiotics regarding improving FD by regulating intestinal flora and provides a reference basis for probiotics to improve FD.
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Affiliation(s)
- Xinyu Shen
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Aijun Xie
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 119077, Singapore;
| | - Zijing Li
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Chengxi Jiang
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Jiaqi Wu
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Mohan Li
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Xiqing Yue
- Shenyang Key Laboratory of Animal Product Processing, Shenyang Agricultural University, Shenyang 110866, China
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12
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Alam MJ, Chen JDZ. Non-invasive neuromodulation: an emerging intervention for visceral pain in gastrointestinal disorders. Bioelectron Med 2023; 9:27. [PMID: 37990288 PMCID: PMC10664460 DOI: 10.1186/s42234-023-00130-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/24/2023] [Indexed: 11/23/2023] Open
Abstract
Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing both abdominal and visceral pain, is a predominant feature, affecting the patients' quality of life and imposing a substantial financial burden on society. Pain signals originating from the gut intricately shape brain dynamics. In response, the brain sends appropriate descending signals to respond to pain through neuronal inhibition. However, due to the heterogeneous nature of the disease and its limited pathophysiological understanding, treatment options are minimal and often controversial. Consequently, many patients with GI disorders use complementary and alternative therapies such as neuromodulation to treat visceral pain. Neuromodulation intervenes in the central, peripheral, or autonomic nervous system by alternating or modulating nerve activity using electrical, electromagnetic, chemical, or optogenetic methodologies. Here, we review a few emerging noninvasive neuromodulation approaches with promising potential for alleviating pain associated with functional dyspepsia, gastroparesis, irritable bowel syndrome, inflammatory bowel disease, and non-cardiac chest pain. Moreover, we address critical aspects, including the efficacy, safety, and feasibility of these noninvasive neuromodulation methods, elucidate their mechanisms of action, and outline future research directions. In conclusion, the emerging field of noninvasive neuromodulation appears as a viable alternative therapeutic avenue for effectively managing visceral pain in GI disorders.
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Affiliation(s)
- Md Jahangir Alam
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
| | - Jiande D Z Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
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13
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Liu X, Wang Y, Shen L, Sun Y, Zeng B, Zhu B, Dai F. Association between frailty and chronic constipation and chronic diarrhea among American older adults: National Health and Nutrition Examination Survey. BMC Geriatr 2023; 23:745. [PMID: 37968629 PMCID: PMC10647084 DOI: 10.1186/s12877-023-04438-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 10/29/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND This study was to explore the relationship between chronic constipation, chronic diarrhea, and frailty in older Americans. METHODS This cross-sectional study selected a total of 4241 community-dwelling individuals aged 60 years and older from the 2005-2010 National Health and Nutrition Examination Survey. Frailty was measured using a 49-item frailty index, and a frailty index > 0.21 was defined as a frail status. Chronic constipation and chronic diarrhea were defined as the "usual or most common type of stool" by the Bristol Stool Form Scale (BSFS) Types 1 and 2 and BSFS Types 6 and 7, respectively. Weighted logistic regression analysis was used to examine the relationship between gut health and frailty status. Restricted cubic spline (RCS) curves were built to assess the association between frailty index and stool frequency. RESULTS Frailty status was associated with higher odds of constipation in an unadjusted model; however, after further adjusting for confounding variables, the relationship between frailty status and constipation was not statistically significant. We discovered a positive correlation between the frailty status and diarrhea after adjustment for all variables. The frailty index showed a U-shaped relationship with stool frequency, and the frailty index was the smallest at a frequency of 10 stools/week. CONCLUSION Negative associations were observed between frailty status and chronic constipation and diarrhea among older adults. Older adults who have a bowel movement frequency of about 10 times per week are the least frail. Future studies are warranted to confirm the causal relationship in this association.
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Affiliation(s)
- Xuna Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Yiwen Wang
- Xi'an International Medical Center Hospital Affiliated To Northwest University, Xi'an, 710119, China
| | - Lin Shen
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Yating Sun
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Beibei Zeng
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Boxu Zhu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Fei Dai
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
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Salmeri N, Sinagra E, Dolci C, Buzzaccarini G, Sozzi G, Sutera M, Candiani M, Ungaro F, Massimino L, Danese S, Mandarino FV. Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review. Microorganisms 2023; 11:2089. [PMID: 37630649 PMCID: PMC10458414 DOI: 10.3390/microorganisms11082089] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.
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Affiliation(s)
- Noemi Salmeri
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Carolina Dolci
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giovanni Buzzaccarini
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giulio Sozzi
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Miriam Sutera
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Massimo Candiani
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
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Kartal B, Sahiner IT. Red Cell Distribution Width, Mean Platelet Volume, and Neutrophil/Lymphocyte Ratio in Patients With Irritable Bowel Syndrome. Cureus 2023; 15:e44496. [PMID: 37791223 PMCID: PMC10544483 DOI: 10.7759/cureus.44496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2023] [Indexed: 10/05/2023] Open
Abstract
Introduction Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by persistent abdominal pain and variable bowel patterns, impacting individuals' quality of life. Despite its functional nature, recent research has indicated the role of inflammatory processes in IBS development. This study aims to investigate the potential diagnostic value of routine blood parameters and their relationship with IBS. Methods In this retrospective analysis, patients diagnosed with IBS based on the ROME IV criteria were identified from the outpatient clinic of Hitit University Erol Olçok Teaching and Research Hospital between January 1, 2023, and May 1, 2023. Exclusion criteria encompassed specific medical conditions, psychiatric disorders, and organic bowel pathologies. A cohort of 100 IBS patients and 100 healthy controls were included for comparison. Comprehensive blood data, including neutrophil count, lymphocyte count, hemoglobin level, red cell distribution width (RDW), mean corpuscular volume (MCV), mean platelet volume (MPV), and platelet count, were collected. Statistical analyses were conducted using SPSS for Windows version 26.0 (IBM Corp., Armonk, NY). Descriptive statistics, Pearson's or Spearman's correlation coefficients, Mann-Whitney U test, and Chi-square test were used to analyze data. Results The study cohort consisted of 70 men (35%) and 130 women (65%). The average age was 51.65 ± 14.64 years (52 years). The mean neutrophil count was 4.6 ± 1.5 (4.29) in the control group and 4.7 ± 2.03 (4.12) in the IBS group. The mean lymphocyte count was 2.3 ± 0.86 (2.21) in the control group and 2.3 ± 0.82 (2.23) in the IBS group, indicating no statistically significant difference (p = 0.732). The mean RDW was measured as 13.62 ± 1.07 (13.4) in the control group and 13.68 ± 1.18 (13.55) in the IBS group, again demonstrating no significant difference (p = 0.915). Mean MCV and MPV values showed no substantial variation between the control and IBS groups (p = 0.649 and p = 0.406, respectively). Conclusion While this study did not yield statistically robust outcomes, it underscores the potential of utilizing neutrophil-to-lymphocyte ratio (NLR), RDW, and MPV as adjunctive diagnostic markers for IBS. These routine and cost-effective parameters could enhance the diagnostic process, especially in cases with suspected IBS. Continued research is essential to unravel their complete diagnostic potential and clinical applicability.
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Kumei S, Ishioh M, Nozu T, Okumura T. Prostaglandin I 2 suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats. Biochim Biophys Acta Gen Subj 2023; 1867:130344. [PMID: 36889449 DOI: 10.1016/j.bbagen.2023.130344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/30/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023]
Abstract
In this study, we attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Since fecal 1-MNA is known for a marker of dysbiosis, we examined the composition of fecal microbiota by T-RFLP analysis. The proportion of clostridium cluster XI, XIVa and XVIII was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in IBS rats. These results suggest for the first time that PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.
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Affiliation(s)
- Shima Kumei
- Department of General Medicine, Asahikawa Medical University, Japan
| | - Masatomo Ishioh
- Department of General Medicine, Asahikawa Medical University, Japan; Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Tsukasa Nozu
- Department of Regional Medicine and Education, Asahikawa Medical University, Japan
| | - Toshikatsu Okumura
- Department of General Medicine, Asahikawa Medical University, Japan; Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan.
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17
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Konstantis G, Efstathiou S, Pourzitaki C, Kitsikidou E, Germanidis G, Chourdakis M. Efficacy and safety of probiotics in the treatment of irritable bowel syndrome: A systematic review and meta-analysis of randomised clinical trials using ROME IV criteria. Clin Nutr 2023; 42:800-809. [PMID: 37031468 DOI: 10.1016/j.clnu.2023.03.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/18/2023] [Accepted: 03/25/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder which affects a great number of patients globally. Clinical trials and meta-analyses have evaluated different therapies for IBS. Some of them have shown that probiotics play a significant role in the management of IBS-patients. Nevertheless, results are controversial, and the efficacy of the administration of probiotics remains to be confirmed, especially in regard to which type of probiotic-strains are beneficial. AIM The aim of the present meta-analysis is to assess the efficacy and safety of the administration of probiotics to IBS-patients with a diagnosis based on Rome IV criteria, which is performed for the first time. METHODS Electronic databases (Pubmed, Scopus and Cochrane) were searched until 26.01.2023 for randomized controlled trials (RCTs) studying the administration of probiotics in adult IBS-patients, who were categorized according to the Rome IV criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (ROB) 2.0. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcomes were the decrease of IBS-Symptom Severity Score (IBS-SSS) and decrease of abdominal pain. The secondary outcomes were the improvement in quality of life (QoL) and the decrease of bloating. Lastly, the adverse effects of probiotics were evaluated. The protocol of the study has been registered at protocols.io (DOI dx.doi.org/10.17504/protocols.io.14egn218yg5d/v1). RESULTS Six double-blind (N = 970) placebo-control RCTs fulfilled the inclusion criteria and overall, nine different strains of probiotics were examined. No significant reduction in IBS-SSS (WMD -43.2, 95% CI -87.5 to 1.0, I2 = 82.9%) was demonstrated, whereas a significant decrease regarding abdominal pain (SMD -0.94, 95% CI -1.53 to -0.35, I2 = 92,2) was shown. Furthermore, no correlation between improvement of QoL and the use of probiotics (SMD -0.64, 95% CI -1.27 to 0.00, I2 = 93,9%) was shown. However, probiotics were associated with a significant reduction in bloating (SMD -0.28, 95% CI -0.47 to -0.09, I2 = 36,0%). A qualitative synthesis was conducted about adverse events and showed that the use of probiotics' is safe without severe adverse events. CONCLUSIONS The administration of probiotics to IBS-patients demonstrated a positive effect on pain and bloating, but due to significant heterogeneity and confounding factors, that were not examined in the included studies, a definitive statement cannot be made. Moreover, probiotics did not lead to an improvement in other parameters. There is a need for larger RCTs in IBS-patients diagnosed according to Rome IV (not III) criteria and especially it is essential to be conducted RCTs which examine the administration of specific strains and have similar methodological characteristics.
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Affiliation(s)
- Georgios Konstantis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Stylianos Efstathiou
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Chryssa Pourzitaki
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Elisavet Kitsikidou
- Department of Internal Medicine, Evangelical Hospital Dusseldorf, Dusseldorf, Germany
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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18
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Koo HS, Son HC, Lee HS, Goong HJ, Kim JS, Kim KB, Kwon YH, Kim JH, Shin HD, Shin JE, Jee SR. Survey-Based Analysis of the Clinical Treatment Status of Irritable Bowel Syndrome in Korea. J Korean Med Sci 2023; 38:e126. [PMID: 37096309 PMCID: PMC10125791 DOI: 10.3346/jkms.2023.38.e126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 01/06/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND The quality-of-life of patients with irritable bowel syndrome is low; incorrect diagnosis/treatment causes economic burden and inappropriate consumption of medical resources. This survey-based study aimed to analyze the current status of irritable bowel syndrome treatment to examine differences in doctors' perceptions of the disease, and treatment patterns. METHODS From October 2019 to February 2020, the irritable bowel syndrome and Intestinal Function Research Study Group of the Korean Society of Neurogastroenterology and Motility conducted a survey on doctors working in primary, secondary, and tertiary healthcare institutions. The questionnaire included 37 items and was completed anonymously using the NAVER platform (a web-based platform), e-mails, and written forms. RESULTS A total of 272 doctors responded; respondents reported using the Rome IV diagnostic criteria (amended in 2016) for diagnosing and treating irritable bowel syndrome. Several differences were noted between the primary, secondary, and tertiary physicians' groups. The rate of colonoscopy was high in tertiary healthcare institutions. During a colonoscopy, the necessity of random biopsy was higher among physicians who worked at tertiary institutions. 'The patient did not adhere to the diet' as a reason for ineffectiveness using low-fermentable oligo-, di-, and mono-saccharides, and polyols diet treatment was higher among physicians in primary/secondary institutions, and 'There are individual differences in terms of effectiveness' was higher among physicians in tertiary institutions. In irritable bowel syndrome constipation predominant subtype, the use of serotonin type 3 receptor antagonist (ramosetron) and probiotics was higher in primary/secondary institutions, while serotonin type 4 receptor agonist was used more in tertiary institutions. In irritable bowel syndrome diarrhea predominant subtype, the use of antispasmodics was higher in primary/secondary institutions, while the use of serotonin type 3 receptor antagonist (ramosetron) was higher in tertiary institutions. CONCLUSION Notable differences were observed between physicians in primary/secondary and tertiary institiutions regarding the rate of colonoscopy, necessity of random biopsy, the reason for the ineffectiveness of low-fermentable oligo-, di-, and mono-saccharides, and polyols diet, and use of drug therapy in irritable bowel syndrome. In South Korea, irritable bowel syndrome is diagnosed and treated according to the Rome IV diagnostic criteria, revised in 2016.
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Affiliation(s)
- Hoon Sup Koo
- Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea
| | - Hui Chang Son
- Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea
| | - Hong Sub Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Hyeon Jeong Goong
- Department of Internal Medicine, Soonchunhyang University Hospital, Bucheon, Korea
| | - Ju Seok Kim
- Chungnam National University School of Medicine, Daejeon, Korea
| | - Ki Bae Kim
- Chungbuk National University Hospital, College of Medicine, Cheongju, Korea
| | - Yong Hwan Kwon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Hak Kim
- Department of Internal Medicine, Dongguk University College of Medicine, Goyang, Korea
| | - Hyun Deok Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Ji Eun Shin
- Department of Biomedical Informatics, Konyang University, College of Medicine, Daejeon, Korea
| | - Sam Ryong Jee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea.
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Dimitrova-Yurukova D, Boyanov N, Nakov V, Nakov R. Diagnosis and management of irritable bowel syndrome-like symptoms in ulcerative colitis. Folia Med (Plovdiv) 2022; 64:733-739. [PMID: 36876537 DOI: 10.3897/folmed.64.e66075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/29/2021] [Indexed: 03/07/2023] Open
Abstract
Both ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) conditions that show some typical features. Persistent GI symptoms typical for IBS are observed in patients with diagnosed UC. Both IBS and UC are characterised by dysregulation of the enteric nervous system, alterations in the gut flora, low-grade mucosal inflammation, and activation of the brain-gut axis. Therefore, it appears that there may be some overlap between the two conditions. It is rather difficult to tell if the lower gastrointestinal symptoms are secondary to coexisting IBS or a hidden UC condition.
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Affiliation(s)
| | - Nikola Boyanov
- Department of Gastroenterology, Pulmed University Hospital, Plovdiv, Bulgaria
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20
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van Megen F, Skodje GI, Lergenmuller S, Zühlke S, Aabakken L, Veierød MB, Henriksen C, Lundin KEA. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms-A Randomized Controlled Trial. Clin Gastroenterol Hepatol 2022; 20:2258-2266.e3. [PMID: 35051648 DOI: 10.1016/j.cgh.2022.01.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/02/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet is an established treatment for irritable bowel syndrome (IBS). We have assessed the efficacy of a moderately low FODMAP diet on persistent symptoms in treated celiac patients. METHODS A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)-IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. Participants were randomized to a low FODMAP-gluten-free diet (intervention) or usual gluten-free diet (control). The GSRS-IBS score was recorded at baseline and at weeks 1 to 4, and the Celiac Symptom Index at baseline and at week 4. Statistics included marginal models for repeated data and analyses of covariance. RESULTS We included 34 participants in the intervention group and 36 in the control group. Time development of GSRS-IBS total scores differed significantly between the groups (Pinteraction < .001), evident after 1 week (mean difference in intervention vs control, -8.2; 95% CI, -11.5 to -5.0) and persisting through week 4 (mean difference in intervention vs control, -10.8; 95% CI, -14.8 to -6.8). Moreover, significantly lower scores were found for the dimensions of pain, bloating, diarrhea, and satiety (Pinteraction ≤ .04), but not constipation (Pinteraction = .43). FODMAP intake during the intervention was moderately low (mean, 8.1 g/d; 95% CI, 6.7-9.3 g/d). The Celiac Symptom Index was significantly lower in the intervention group at week 4 (mean difference, -5.8; 95% CI, -9.6 to -2.0). CONCLUSIONS A short-term moderately low FODMAP diet significantly reduced gastrointestinal symptoms and increased celiac disease-specific health, and should be considered for the management of persistent symptoms in celiac disease. CLINICALTRIALS gov: NCT03678935.
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Affiliation(s)
- Frida van Megen
- Department of Clinical Services, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, Oslo, Norway; K.G. Jebsen Coeliac Disease Research Centre, Oslo, Norway.
| | - Gry I Skodje
- Department of Nutrition, Institute of Basic Medical Sciences, Oslo, Norway; Healthy Life Centre, Municipality of Nes, Årnes, Norway
| | - Simon Lergenmuller
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | | | - Lars Aabakken
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Marit B Veierød
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Christine Henriksen
- Department of Nutrition, Institute of Basic Medical Sciences, Oslo, Norway; K.G. Jebsen Coeliac Disease Research Centre, Oslo, Norway
| | - Knut E A Lundin
- K.G. Jebsen Coeliac Disease Research Centre, Oslo, Norway; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
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Shi YZ, Ye K, Chen M, Xie X, Fan XY, Xie CR, Tao QF, Hua C, Wu QP, Jiang XH, Wan YY, Li ZG, Zheng H, Yu SG. Acupuncture for irritable bowel syndrome: study protocol of a prospective, multicentre, registry study in real-world settings. Eur J Integr Med 2022. [DOI: 10.1016/j.eujim.2022.102145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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22
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Capozza M, Laforgia N, Rizzo V, Salvatore S, Guandalini S, Baldassarre M. Probiotics and Functional Gastrointestinal Disorders in Pediatric Age: A Narrative Review. Front Pediatr 2022; 10:805466. [PMID: 35252059 PMCID: PMC8888932 DOI: 10.3389/fped.2022.805466] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Assessment and management of pain are essential components of pediatric care. Pain in pediatric age is characterized by relevant health and socio-economic consequences due to parental concern, medicalization, and long-term physical and psychological impact in children. Pathophysiological mechanisms of nociception include several pathways in which also individual perception and gut-brain axis seem to be involved. In this narrative review, we analyze the rational and the current clinical findings of probiotic use in the management of functional gastrointestinal disorders (FGID) in pediatric age, with special focus on infantile colic, irritable bowel syndrome, constipation, and gastroesophageal reflux. Some specific probiotics showed a significant reduction in crying and fussing compared to placebo in breastfed infants with colic, although their exact mechanism of action in this disorder remains poorly understood. In irritable bowel syndrome, a limited number of studies showed that specific strains of probiotics can improve abdominal pain/discomfort and bloating/gassiness, although data are still scarce. As for constipation, whilst some strains appear to reduce the number of hard stools in constipated children, the evidence is not adequate to support the use of probiotics in the management of functional constipation. Similarly, although some probiotic strains could promote gastric emptying with a potential improvement of functional symptoms related to gastroesophageal reflux, current evidence is insufficient to provide any specific recommendation for the prevention or treatment of gastroesophageal reflux. In conclusion, probiotics have been proposed as part of management of pain in functional gastrointestinal disorders in pediatric age, but mechanisms are still poorly understood and evidence to guide clinical practice is currently inadequate.
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Affiliation(s)
- Manuela Capozza
- Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari “Aldo Moro”, Bari, Italy
| | - Nicola Laforgia
- Section of Neonatology and Neonatal Intensive Care Unit, Interdisciplinary Department of Medicine (DIM), University of Bari “Aldo Moro”, Bari, Italy
| | - Valentina Rizzo
- Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari “Aldo Moro”, Bari, Italy
| | - Silvia Salvatore
- Department of Pediatrics, University of Insubria, Ospedale “F. Del Ponte”, Varese, Italy
| | - Stefano Guandalini
- Section of Gastroenterology, Department of Pediatrics, Hepatology and Nutrition University of Chicago, Chicago, IL, United States
| | - Mariella Baldassarre
- Section of Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology (DIMO), University of Bari “Aldo Moro”, Bari, Italy
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Münch A, Mihaly E, Nagy F, Madisch A, Kupčinskas J, Miehlke S, Bohr J, Bouma G, Guardiola J, Belloc B, Shi C, Aust D, Mohrbacher R, Greinwald R, Munck LK. Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial. United European Gastroenterol J 2021; 9:837-847. [PMID: 34414678 PMCID: PMC8435258 DOI: 10.1002/ueg2.12131] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/01/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIMS Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi. METHODS Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8. RESULTS Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase. CONCLUSIONS Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.
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Affiliation(s)
- Andreas Münch
- Department of Gastroenterology and HepatologyLinköping University Hospital School of MedicineLinköpingSweden
| | - Emese Mihaly
- Department of Internal MedicineSemmelweis EgyetemBudapestHungary
| | - Ferenc Nagy
- First Department of MedicineSzegedi Egyetem ÁOK I sz.SzegedHungary
| | - Ahmed Madisch
- Medical Department IKRH Klinikum SiloahHannoverGermany
| | - Juozas Kupčinskas
- Department of GastroenterologyInstitute for Digestive ResearchLithuanian University of Health SciencesKaunasLithuania
| | - Stephan Miehlke
- Center for Digestive DiseasesInternal Medicine Center EppendorfHamburgGermany
- Centre for Interdisciplinary EndoscopyUniversity Hospital EppendorfHamburgGermany
| | - Johan Bohr
- Division of GastroenterologyDepartment of MedicineÖrebro University HospitalÖrebroSweden
| | - Gerd Bouma
- Department of GastroenterologyVrije Universiteit Medical CentreAmsterdamNetherlands
| | - Jordi Guardiola
- Department of Digestive DiseasesHospital Universitario de BellvitgeBarcelonaSpain
| | - Blanca Belloc
- Department of GastroenterologyHospital San Jorge – University of ZaragozaHuescaSpain
| | - Chunliang Shi
- Department of GastroenterologyNorrlands UniversitetssjukhusUmeåSweden
| | - Daniela Aust
- Institute for PathologyUniversity Hospital Carl Gustav CarusDresdenGermany
| | - Ralf Mohrbacher
- Clinical Research and Development DepartmentDr Falk Pharma GmbHFreiburgGermany
| | - Roland Greinwald
- Clinical Research and Development DepartmentDr Falk Pharma GmbHFreiburgGermany
| | - Lars Kristian Munck
- Department of GastroenterologyZealand University HospitalKøgeDenmark
- Department of Clinical MedicineUniversity of CopenhagenCopenhagenDenmark
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Shi X, Hu Y, Zhang B, Li W, Chen JD, Liu F. Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation. JCI Insight 2021; 6:e150052. [PMID: 34138761 PMCID: PMC8410029 DOI: 10.1172/jci.insight.150052] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/16/2021] [Indexed: 12/28/2022] Open
Abstract
BackgroundAbdominal pain and constipation are 2 main symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to investigate the effects and possible mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) in patients with IBS-C.MethodsForty-two patients with IBS-C were randomized into a 4-week sham-taVNS or taVNS treatment. The primary outcomes were complete spontaneous bowel movements per week (CSBMs/week) and visual analog scale (VAS) for abdominal pain. High-resolution anorectal manometry (HRAM) was performed to evaluate anorectal motor and sensory function. Cytokines and brain gut peptides were analyzed in blood samples. ECG was recorded for the assessment of autonomic function.ResultsCompared with sham-taVNS, (a) taVNS increased CSBMs/week (P = 0.001) and decreased VAS pain score (P = 0.001); (b) improved quality of life (P = 0.020) and decreased IBS symptom score (P = 0.001); (c) improved rectoanal inhibitory reflex (P = 0.014) and improved rectal sensation (P < 0.04); (d) decreased a number of proinflammatory cytokines and serotonin in circulation; and (e) enhanced vagal activity (P = 0.040). The vagal activity was weakly correlated with the CSBMs/week (r = 0.391; P = 0.010) and the VAS pain score (r = -0.347; P = 0.025).ConclusionsNoninvasive taVNS improves both constipation and abdominal pain in patients with IBS-C. The improvement in IBS-C symptoms might be attributed to the integrative effects of taVNS on intestinal functions mediated via the autoimmune mechanisms.Trial registrationwww.chictr.org.cn, no. ChiCTR2000029644.FundingNational Natural Science Foundation of China (grant no. 81970538 for FL).
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Affiliation(s)
- Xiaodan Shi
- Department of Gastroenterology, Shanghai East Hospital affiliated to Tongji University, Shanghai, China
| | - Yedong Hu
- Department of Gastroenterology, Shanghai East Hospital affiliated to Tongji University, Shanghai, China
| | - Bo Zhang
- Department of Gastroenterology, the 928th Hospital of the PLA Joint Logistics Support Force, Haikou, Hainan, China
| | - Wenna Li
- Department of Gastroenterology, Shanghai East Hospital affiliated to Tongji University, Shanghai, China
| | - Jiande Dz Chen
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Fei Liu
- Department of Gastroenterology, Shanghai East Hospital affiliated to Tongji University, Shanghai, China
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Jones J, Lembo A, Heidelbaugh J, Kuritzky L, Lacy B. Management of irritable bowel syndrome with diarrhea: focus on eluxadoline. Curr Med Res Opin 2021; 37:567-578. [PMID: 33566707 DOI: 10.1080/03007995.2021.1888705] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE We sought to summarize current recommendations for the diagnosis of diarrhea-predominant irritable bowel syndrome (IBS-D) and describe available management options, highlighting a newer US Food and Drug Administration (FDA)-approved agent, eluxadoline. METHODS Literature on IBS-D was assessed up to January 2020 using PubMed, with key search terms including "IBS-D diagnosis", "IBS-D management", and "eluxadoline". RESULTS IBS is a common gastrointestinal disorder affecting up to 14% of US adults and is particularly prevalent in women and those aged under 50. Symptoms include abdominal pain associated with altered bowel habits (i.e. diarrhea and/or constipation subtyped based on the predominant stool pattern). As IBS-D is challenging to manage with varying symptom severity, effective treatment requires a personalized management approach. Evidence-based therapeutic options endorsed by the American Gastroenterological Association and the American College of Gastroenterology can be used to effectively guide treatment. Dietary and lifestyle modifications, including adequate hydration, reducing caffeine and alcohol intake, and increasing soluble fiber intake may lead to symptom improvement. Over-the-counter medications such as loperamide are frequently recommended and may improve stool frequency and rectal urgency; however, for the outcome of abdominal pain, mixed results have been observed. Several off-label prescription medications are useful in IBS-D management, including tricyclic antidepressants, bile acid sequestrants, and antispasmodics. Three prescription medications have been approved by the FDA for IBS-D: alosetron, eluxadoline, and rifaximin. CONCLUSIONS IBS-D can be effectively managed in the primary care setting in the absence of alarm features. Benefits and risks of pharmacologic interventions should be weighed during treatment selection.
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Affiliation(s)
- Jennifer Jones
- UCF College of Medicine, HCA Consortium Family Medicine Residency, Gainesville, FL, USA
| | - Anthony Lembo
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Joel Heidelbaugh
- Departments of Family Medicine and Urology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Louis Kuritzky
- Department of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Brian Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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The Interrelationships between Intestinal Permeability and Phlegm Syndrome and Therapeutic Potential of Some Medicinal Herbs. Biomolecules 2021; 11:biom11020284. [PMID: 33671865 PMCID: PMC7918952 DOI: 10.3390/biom11020284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 02/06/2021] [Accepted: 02/10/2021] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal (GI) tract has an intriguing and critical role beyond digestion in both modern and complementary and alternative medicine (CAM), as demonstrated by its link with the immune system. In this review, we attempted to explore the interrelationships between increased GI permeability and phlegm, an important pathological factor in CAM, syndrome, and therapeutic herbs for two disorders. The leaky gut and phlegm syndromes look considerably similar with respect to related symptoms, diseases, and suitable herbal treatment agents, including phytochemicals even though limitations to compare exist. Phlegm may be spread throughout the body along with other pathogens via the disruption of the GI barrier to cause several diseases sharing some parts of symptoms, diseases, and mechanisms with leaky gut syndrome. Both syndromes are related to inflammation and gut microbiota compositions. Well-designed future research should be conducted to verify the interrelationships for evidence based integrative medicine to contribute to the promotion of public health. In addition, systems biology approaches should be adopted to explore the complex synergistic effects of herbal medicine and phytochemicals on conditions associated with phlegm and leaky gut syndromes.
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Effect of Heat-killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome. Nutrients 2021; 13:nu13020568. [PMID: 33572194 PMCID: PMC7915558 DOI: 10.3390/nu13020568] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/02/2021] [Accepted: 02/06/2021] [Indexed: 02/06/2023] Open
Abstract
Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.
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28
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Norlin AK, Walter S, Icenhour A, Keita ÅV, Elsenbruch S, Bednarska O, Jones MP, Simon R, Engström M. Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity. Brain Behav Immun 2021; 92:211-222. [PMID: 33249172 DOI: 10.1016/j.bbi.2020.11.035] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 10/17/2020] [Accepted: 11/23/2020] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a symptom-based disorder of gut-brain interactions generating abdominal pain. It is also associated with a vulnerability to develop extraintestinal symptoms, with fatigue often reported as one of the most disturbing. Fatigue is related to brain function and inflammation in several disorders, however, the mechanisms of such relations in IBS remain elusive. This study aimed to elucidate fatigue and its association with a resting state network of mesocorticolimbic regions of known importance in fatigue, and to explore the possible role of circulating TNF-α levels in IBS and healthy controls (HC). Resting state functional magnetic resonance imaging (fMRI) was conducted in 88 IBS patients and 47 HC of similar age and gender to investigate functional connectivity between mesocorticolimbic regions. Further, fatigue impact on daily life and plasma levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), of known relevance to immune activation in IBS, were also measured. The selected mesocorticolimbic regions indeed formed a functionally connected network in all participants. The nucleus accumbens (NAc), in particular, exhibited functional connectivity to all other regions of interest. In IBS, fatigue impact on daily life was negatively correlated with the connectivity between NAc and dorsolateral prefrontal cortex bilaterally (left p = 0.019; right p = 0.038, corrected for multiple comparisons), while in HC, fatigue impact on daily life was positively correlated to the connectivity between the right NAc and anterior middle insula in both hemispheres (left p = 0.009; right p = 0.011). We found significantly higher levels of TNF-α in IBS patients compared to HC (p = 0.001) as well as a positive correlation between TNF-α and fatigue impact on daily life in IBS patients (rho = 0.25, p = 0.02) but not in HC (rho = -0.13, p = 0.37). There was no association between functional connectivity in the mesocorticolimbic network and plasma levels of TNF-α in either group In summary, this novel multimodal study provides the first evidence that the vulnerability to fatigue in IBS is associated with connectivity within a mesocorticolimbic network as well as immune activation. These findings warrant further investigation, both peripherally and potentially with measurements of central immune activation as well.
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Affiliation(s)
- Anna-Karin Norlin
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
| | - Susanna Walter
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Adriane Icenhour
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping Sweden; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Åsa V Keita
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Olga Bednarska
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Michael P Jones
- Department of Psychology, Macquarie University, Sydney, Australia
| | - Rozalyn Simon
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping Sweden
| | - Maria Engström
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping Sweden
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Kumari MV, Amarasiri L, Rajindrajith S, Devanarayana NM. Functional abdominal pain disorders and asthma: two disorders, but similar pathophysiology? Expert Rev Gastroenterol Hepatol 2021; 15:9-24. [PMID: 32909837 DOI: 10.1080/17474124.2020.1821652] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/07/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Functional abdominal pain disorders (FAPDs) and asthma are common ailments affecting both children and adults worldwide. Multiple studies have demonstrated an association between these two disorders. However, the exact reason for this observed association is not apparent. AREAS COVERED The current review has explored available literature and outlined multiple underlying pathophysiological mechanisms, common to both asthma and FAPDs, as possible reasons for this association. EXPERT OPINION Smooth muscle dysfunction, hypersensitivity and hyper-responsiveness, mucosal inflammation, and barrier dysfunction involving gastrointestinal and respiratory tracts are the main underlying pathophysiological mechanisms described for the generation of symptoms in FAPDs and asthma. In addition, alterations in neuroendocrine regulatory functions, immunological dysfunction, and microbial dysbiosis have been described in both disorders. We believe that the pathophysiological processes that were explored in this article would be able to expand the mechanisms of the association. The in-depth knowledge is needed to be converted to therapeutic and preventive strategies to improve the quality of care of children suffering from FAPDs and asthma.
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Affiliation(s)
- Manori Vijaya Kumari
- Department of Physiology, Faculty of Medicine & Allied Sciences, Rajarata University of Sri Lanka , Anuradhapura, Sri Lanka
| | - Lakmali Amarasiri
- Department of Physiology, Faculty of Medicine, University of Colombo , Colombo, Sri Lanka
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Li C, Shuai Y, Zhou X, Chen H. Association between Helicobacter pylori infection and irritable bowel syndrome: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e22975. [PMID: 33327230 PMCID: PMC7738067 DOI: 10.1097/md.0000000000022975] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND In recent years, the incidence of IBS has gradually increased, and it is considered as one of the most common functional gastrointestinal diseases. However, the etiology of IBS is still unclear, and expectations are rising for more targeted treatments. Many clinical trials have explored the link between Helicobacter pylori (H pylori) and IBS, with different conclusions. Therefore, we conducted a meta-analysis to explore whether there is an association between H pylori and IBS, which is of great significance for targeted treatment of IBS. METHODS We performed a systematic review and meta-analysis of the association between H pylori and IBS. We searched PubMed, EMBASE, Medline and the Cochrane Library to collect related studies. OR was used to describe the ratio of the probability of the H pylori infection occurring in IBS patients versus the controls. Heterogeneity was assessed by subgroup and meta-regression analysis. RESULTS Eight studies, including 1861 patients, assessed the association between H pylori infection and IBS. The OR of H pylori in IBS patients compared to controls was 1.32 (95% CI: 0.94-1.87; P = 0.11). Subgroup analyses showed a difference between IBS patients diagnosed with Roman III criteria and those diagnosed with non-Roman III criteria. CONCLUSIONS Our study suggests that H pylori may have a positive effect on the development of IBS. Although the differences were not statistically significant, there were significant differences among subgroups of patients. Considering the limitations and heterogeneity, high quality studies are needed to further explore the effect of H pylori on the development of IBS.
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Affiliation(s)
- Chenyu Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
- First Clinical Medical College, Nanchang University, Nanchang, China
| | - Yujun Shuai
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
- First Clinical Medical College, Nanchang University, Nanchang, China
| | - Xiaodong Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
| | - Hongxia Chen
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanchang University
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Guo J, Pei L, Chen L, Chen H, Gu D, Peng Y, Sun J. Bidirectional association between irritable bowel syndrome and restless legs syndrome: a systematic review and meta-analysis. Sleep Med 2020; 77:104-111. [PMID: 33348297 DOI: 10.1016/j.sleep.2020.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 11/03/2020] [Accepted: 12/01/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Several observational studies have shown that patients with irritable bowel syndrome (IBS) may have a high risk of restless legs syndrome (RLS). This systematic review and meta-analysis aimed to comprehensively investigate the bidirectional association between IBS and RLS. METHODS All conservational studies on IBS and RLS were searched in MEDLINE (assessed by PubMed), Embase, Web of Science, CINAHL, the Cochrane Library database and Google Scholar from inception to June 14, 2020. The Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality were used to assess the methodological quality of the cohort and cross-sectional studies, respectively. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using Reviewer Manager 5.3. RESULT A total of five cross-sectional studies of moderate methodological quality and one cohort study of high methodological quality were included in our review. Four cross-sectional studies and one cohort study involving 86 438 individuals met the criteria of IBS predicating the onset of RLS. Patients with IBS had a nearly three-fold increased odds of RLS compared with controls (OR = 2.60, 95%CI: 2.17-3.12, P < 0.00001; I2 = 48%, P = 0.11). Three sensitivity analyses confirmed the robustness of the pooled result. Two cross-sectional studies involving 3581 individuals met the criteria of RLS predicating the onset of IBS. RLS patients had a nearly four-fold increased odds of IBS compared with controls without RLS (OR = 3.87, 95%CI: 1.73-8.66, P = 0.0010; I2 = 77%, P = 0.04). CONCLUSION In this systematic review and meta-analysis, we found a substantial bidirectional association between IBS and RLS. More prospective, high-quality, population-based studies are warranted in the future.
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Affiliation(s)
- Jing Guo
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lixia Pei
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hao Chen
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Dongmei Gu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yongjun Peng
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
| | - Jianhua Sun
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
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Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ. Functional dyspepsia. Lancet 2020; 396:1689-1702. [PMID: 33049222 DOI: 10.1016/s0140-6736(20)30469-4] [Citation(s) in RCA: 266] [Impact Index Per Article: 53.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 01/21/2020] [Accepted: 02/25/2020] [Indexed: 12/13/2022]
Abstract
Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.
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Affiliation(s)
- Alexander C Ford
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.
| | - Sanjiv Mahadeva
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - M Florencia Carbone
- Department of Chronic Diseases, Metabolism and Ageing, University of Leuven, Leuven, Belgium
| | | | - Nicholas J Talley
- Australian Gastrointestinal Research Alliance, University of Newcastle, Newcastle, NSW, Australia
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Effect of a Synbiotic Containing Lactobacillus paracasei and Opuntia humifusa on a Murine Model of Irritable Bowel Syndrome. Nutrients 2020; 12:nu12103205. [PMID: 33092151 PMCID: PMC7594034 DOI: 10.3390/nu12103205] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/14/2020] [Accepted: 10/19/2020] [Indexed: 12/12/2022] Open
Abstract
The administration of a combination of probiotics and prebiotics is expected to be a promising strategy for improving irritable bowel syndrome (IBS) symptoms. This study aimed to investigate the efficacy of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa extract for symptomatic improvement of IBS in a murine model and to evaluate the mechanism underlying the beneficial effects of this synbiotic. A total of 20 male Wistar rats aged 8 weeks with IBS induced by restraint stress were assigned into four groups and administered L. paracasei as a probiotic and O. humifusa extract as a prebiotic for 4 weeks. The primary outcome was stool consistency at week 4. To evaluate the mechanism underlying the beneficial effects of the synbiotic, fecal microbial analysis was conducted, and the serum corticosterone levels, tumor necrosis factor-α (TNF-α) levels in the colon tissue, and expression of tight junction proteins were investigated. All three treatment groups showed significantly lower scores for stool consistency than the control group at week 4 (all p < 0.001). When compared with the control group, the synbiotic groups showed a significantly greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue, and higher expression of tight junction proteins. This novel synbiotic containing L. paracasei and O. humifusa extract can improve the stool consistency in a murine model of IBS. It may be a promising treatment option for IBS, and human studies are warranted.
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Chiaffarino F, Cipriani S, Ricci E, Mauri PA, Esposito G, Barretta M, Vercellini P, Parazzini F. Endometriosis and irritable bowel syndrome: a systematic review and meta-analysis. Arch Gynecol Obstet 2020; 303:17-25. [PMID: 32949284 DOI: 10.1007/s00404-020-05797-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 09/11/2020] [Indexed: 12/15/2022]
Abstract
PURPOSE Irritable bowel disease and endometriosis are two common diseases characterized by chronic inflammation state and recurrent abdominal pain. As a consequence of sharing of symptoms and chronic inflammation, endometriosis and IBS may coexist and be misdiagnosed and this leads to delays in diagnosis, mismanagement, and unnecessary testing. In recent years, some studies have found higher risk of IBS in women with endometriosis, compared to women without endometriosis. To provide a general overview, we performed a systematic review and a meta-analysis on published data on this issue. METHODS By a systematic literature search selection process, 11 studies were identified for the current study: 2 prospective and 2 retrospective cohort studies, 4 case-control studies, 1 cross-sectional study and 2 clinical series. RESULTS When we meta-analysed data about the prevalence of IBS in women with endometriosis, the overall OR (95%CI), compared to women without endometriosis was 3.26 (1.97-5.39) with no statistically significant heterogeneity. All three studies considering the incidence of IBS in women with a previous diagnosis of endometriosis showed about twofold greater risk among women with endometriosis than women without. Likewise, in the random effects model of the meta-analysis, the overall OR of history of IBS in women with endometriosis was 3.10 (95% CI 2.06-4.67), with no heterogeneity between three studies considered. CONCLUSION This meta-analysis provides epidemiological evidence of a link between endometriosis and IBS, highlighting two or more times higher risk of IBS in women with endometriosis compared to women without the condition.
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Affiliation(s)
- Francesca Chiaffarino
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy.
| | - Sonia Cipriani
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
| | - Elena Ricci
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
| | - Paola Agnese Mauri
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy.,Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
| | - Giovanna Esposito
- Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
| | - Marta Barretta
- Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Ospedale Macedonio Melloni, Via Macedonio Melloni 52, 20129, Milan, Italy
| | - Paolo Vercellini
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy.,Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
| | - Fabio Parazzini
- Department of Woman, Newborn and Child, Fondazione Istituto Di Ricovero E Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy.,Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy
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Carco C, Young W, Gearry RB, Talley NJ, McNabb WC, Roy NC. Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis. Front Cell Infect Microbiol 2020; 10:468. [PMID: 33014892 PMCID: PMC7509092 DOI: 10.3389/fcimb.2020.00468] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
The human gastrointestinal tract harbors most of the microbial cells inhabiting the body, collectively known as the microbiota. These microbes have several implications for the maintenance of structural integrity of the gastrointestinal mucosal barrier, immunomodulation, metabolism of nutrients, and protection against pathogens. Dysfunctions in these mechanisms are linked to a range of conditions in the gastrointestinal tract, including functional gastrointestinal disorders, ranging from irritable bowel syndrome, to functional constipation and functional diarrhea. Irritable bowel syndrome is characterized by chronic abdominal pain with changes in bowel habit in the absence of morphological changes. Despite the high prevalence of irritable bowel syndrome in the global population, the mechanisms responsible for this condition are poorly understood. Although alterations in the gastrointestinal microbiota, low-grade inflammation and immune activation have been implicated in the pathophysiology of functional gastrointestinal disorders, there is inconsistency between studies and a lack of consensus on what the exact role of the microbiota is, and how changes to it relate to these conditions. The complex interplay between host factors, such as microbial dysbiosis, immune activation, impaired epithelial barrier function and motility, and environmental factors, including diet, will be considered in this narrative review of the pathophysiology of functional gastrointestinal disorders.
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Affiliation(s)
- Caterina Carco
- School of Food and Advanced Technology, Massey University, Palmerston North, New Zealand.,Riddet Institute, Massey University, Palmerston North, New Zealand.,Food Nutrition and Health Team, AgResearch Grasslands, Palmerston North, New Zealand.,The High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Wayne Young
- Riddet Institute, Massey University, Palmerston North, New Zealand.,Food Nutrition and Health Team, AgResearch Grasslands, Palmerston North, New Zealand.,The High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Richard B Gearry
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | - Warren C McNabb
- Riddet Institute, Massey University, Palmerston North, New Zealand.,The High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Nicole C Roy
- Riddet Institute, Massey University, Palmerston North, New Zealand.,The High-Value Nutrition National Science Challenge, Auckland, New Zealand.,Liggins Institute, University of Auckland, Auckland, New Zealand.,Department of Human Nutrition, University of Otago, Dunedin, New Zealand
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36
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Singh M, Singh V, Schurman JV, Colombo JM, Friesen CA. The relationship between mucosal inflammatory cells, specific symptoms, and psychological functioning in youth with irritable bowel syndrome. Sci Rep 2020; 10:11988. [PMID: 32686762 PMCID: PMC7371888 DOI: 10.1038/s41598-020-68961-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/29/2020] [Indexed: 12/11/2022] Open
Abstract
Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS.
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Affiliation(s)
- Meenal Singh
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
| | - Vivekanand Singh
- Department of Pathology, The University of Texas Southwestern Medical Center, 1935 Medical District Drive, Dallas, TX, 75235, USA
| | - Jennifer V Schurman
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
| | - Jennifer M Colombo
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
| | - Craig A Friesen
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA.
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Wen Y, Li J, Long Q, Yue CC, He B, Tang XG. The efficacy and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis based on seventeen randomized controlled trials. Int J Surg 2020; 79:111-119. [DOI: 10.1016/j.ijsu.2020.04.063] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 04/22/2020] [Accepted: 04/27/2020] [Indexed: 12/18/2022]
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The Effects on Immune Function and Digestive Health of Consuming the Skin and Flesh of Zespri® SunGold Kiwifruit (Actinidia Chinensis var. Chinensis ‘Zesy002’) in Healthy and IBS-Constipated Individuals. Nutrients 2020; 12:nu12051453. [PMID: 32443433 PMCID: PMC7284715 DOI: 10.3390/nu12051453] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/12/2020] [Accepted: 05/14/2020] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that results in constipation (IBS-C) or diarrhoea with abdominal pain, flatulence, nausea and bloating. Kiwifruit (Actinidia spp.) are nutrient-dense fruit with a number of reported health benefits that include lowering glycaemic response, improving cardiovascular and inflammatory biomarkers, and enhancing gut comfort and laxation. This study investigated the effect of consuming three whole Zespri® SunGold kiwifruit (Actinidia chinensis var. chinensis ‘Zesy002’) with or without skin on cytokine production and immune and gut health in healthy people and those with IBS-C symptoms. This study enrolled thirty-eight participants in a 16 week randomized cross-over study (19 healthy and 19 participants with IBS-C). Participants were randomized to consume either three kiwifruit without eating the skin or three kiwifruit including the skin for 4 weeks each, with a 4 week washout in between each intervention. There was a significant decrease in the pro-inflammatory cytokine, TNF-α, for both the healthy and the IBS-C participants when they consumed whole kiwifruit and skin, and also for the healthy participants when they ate whole kiwifruit without the skin (p < 0.001). The kiwifruit interventions increased bowel frequency and significantly reduced the gastrointestinal symptom rating scale constipation and Birmingham IBS pain scores for both participant groups. We have demonstrated that consuming the skin of SunGold kiwifruit might have beneficial effects on gastrointestinal health that are not produced by consuming the flesh alone.
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Berg LK, Goll R, Fagerli E, Ludviksen JK, Fure H, Moen OS, Sørbye SW, Mollnes TE, Florholmen J. Intestinal inflammatory profile shows increase in a diversity of biomarkers in irritable bowel syndrome. Scand J Gastroenterol 2020; 55:537-542. [PMID: 32329383 DOI: 10.1080/00365521.2020.1754455] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Background: It has been proposed that irritable bowel syndrome (IBS) is a low-grade mucosal inflammatory disease.Objective: To characterize the intestinal inflammatory profile in IBS patients with or without fructose intolerance.Design: Patients referred to colonoscopy with IBS complaints were screened for participation. IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were included in the study. One subgroup was patients included in a fructose-reduced diet study for 2 months with effects based on VAS symptom scores. Healthy controls were subjects under investigation of colorectal cancer screening with no IBS or other gastrointestinal diseases. All patients included had normal histology from rectum. Mucosal cytokines, chemokines and growth factors were measured by multiplex technology.Results: Of 27 inflammatory markers tested in the mucosal tissue, 13 were significantly increased and none was significantly decreased in IBS as compared to controls. Significantly increased were the proinflammatory cytokines tumor necrosis factor, the typical TH1 markers IFNγ, IL-1β, IL-2 and RANTES, the typical TH2 markers IL-5 and IL-9, the TH17 marker IL-17, TNF, the pleiotropic IL-15, and the growth factors bFGF and GM-CSF. In IBS patients with fructose intolerance only IL-5 was significantly increased compared to patients without fructose intolerance.Conclusions: A dysregulated mucosal inflammatory profile with an increased level of TH1, TH2 and TH17 markers, and growth factors were observed in bowel mucosa in of IBS patients when compared to healthy controls.
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Affiliation(s)
- Leif Kyrre Berg
- Department of Medicine, Hospital of Helgeland, Mo i Rana, Norway.,Research Group of Gastroenterology and Nutrition, Institute of Clinical Medicine, Norwegian Arctic University, Tromsø, Norway
| | - Rasmus Goll
- Research Group of Gastroenterology and Nutrition, Institute of Clinical Medicine, Norwegian Arctic University, Tromsø, Norway
| | - Erik Fagerli
- Department of Medicine, Hospital of Helgeland, Mo i Rana, Norway
| | - Judith Krey Ludviksen
- Research Laboratory, Nordland Hospital, Bodø, Norway.,K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway
| | - Hilde Fure
- Research Laboratory, Nordland Hospital, Bodø, Norway.,K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway
| | - Odd Sverre Moen
- Research Group of Gastroenterology and Nutrition, Institute of Clinical Medicine, Norwegian Arctic University, Tromsø, Norway
| | - Sveinung W Sørbye
- Clinical Pathology, University Hospital of North Norway, Tromsø, Norway
| | - Tom Eirik Mollnes
- Research Laboratory, Nordland Hospital, Bodø, Norway.,K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.,Department of Immunology, Oslo University Hospital, Oslo, Norway.,K.G. Jebsen JIRC, University of Oslo, Oslo, Norway.,Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
| | - Jon Florholmen
- Research Group of Gastroenterology and Nutrition, Institute of Clinical Medicine, Norwegian Arctic University, Tromsø, Norway
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Robles-Medranda C, Oleas R, Valero M, Puga-Tejada M, Soria-Alcívar M, Ospina J, Alvarado-Escobar H, Muñoz-Jurado G, Baquerizo-Burgos J, Pitanga-Lukashok H. Confocal laser endomicroscopy detects colonic inflammation in patients with irritable bowel syndrome: a prospective study. Endosc Int Open 2020; 8:E550-E557. [PMID: 32258379 PMCID: PMC7089800 DOI: 10.1055/a-1119-6327] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 12/20/2019] [Indexed: 12/17/2022] Open
Abstract
Background and aims Irritable bowel syndrome (IBS) is considered to be a functional disease, but recent data indicate measurable organic alterations. We aimed to determine the presence of colorectal mucosa microinflammation in vivo via probe-confocal laser endomicroscopy (pCLE) and histological evaluation in IBS patients. Methods This was a prospective, controlled, nonrandomized single-blind diagnostic trial performed in a tertiary institution. pCLE images and targeted biopsy of each colon segment obtained during colonoscopies of IBS patients and controls were analyzed for inflammatory changes. Biopsies were classified using the Geboes scale, and the odds ratio and overall diagnostic accuracy were calculated. Results During the 15-month study period, 37 patients were allocated to each group. The mean age was 53.1 ± 14.3 years; 64.9 % were female. Signs of colonic mucosa inflammation were evident on 65.8 % of pCLE images from IBS patients compared to 23.4 % of images from controls (OR 6.28; 4.14-9.52; P < 0.001). In total, 20/37 patients had microinflammation via pCLE in ≥ 3 colon segments in the IBS group, compared to 1/37 in the control group. A Geboes score > 0 was attributed to 60.8 % of biopsies from patients in the IBS group compared to 27.5 % of biopsies from the control group. The sensitivity, specificity, positive and negative predictive values, observed and interrater agreement of pCLE-detected inflammatory changes in IBS using histology as gold standard were 76 %, 91 %, 76 %, 91 %, 86.5 %, and 66.8 %, respectively. Conclusions Patients with IBS have a six-fold higher prevalence of colorectal mucosa microinflammation than healthy controls. pCLE might be a reliable method to detect colorectal mucosa microinflammation in IBS patients.
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Affiliation(s)
- Carlos Robles-Medranda
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Roberto Oleas
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Manuel Valero
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Miguel Puga-Tejada
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Miguel Soria-Alcívar
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Jesenia Ospina
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Haydee Alvarado-Escobar
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Guillermo Muñoz-Jurado
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Jorge Baquerizo-Burgos
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Hannah Pitanga-Lukashok
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
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Karatay E, Utku ÖG. Serum resolvin D1 levels as a marker of inflammation in constipation dominant irritable bowel syndrome. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:113-119. [PMID: 32141819 DOI: 10.5152/tjg.2020.19751] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS The objective of this study is to determine the role of circulating resolvin D1 (RvD1) in patients with constipation subtype of irritable bowel syndrome (IBS-C) and evaluate the relationship between abdominal pain severity and RvD1 levels. MATERIALS AND METHODS This research included 55 patients with IBS-C and 36 healthy controls. Controls were selected from patients who applied to our department with similar complaints as IBS but were not diagnosed with any type of pathology after further investigations. All participants underwent complete blood count, C-reactive protein (CRP), and RvD1 levels measurements. We also recorded abdominal pain severity and the number of bowel movements. Patients with IBS-C were compared with respect to the demographic features and laboratory measurements. RESULTS The median CRP concentration in patients with IBS-C was significantly higher than that of controls (p=0.003). However, the median RvD1 concentration was significantly lower in the IBS group than that of the control group (p<0.001). The receiver operating characteristic curve analyses revealed that RvD1 concentration lower than 0.47 ng/mL and CRP concentration higher than 3.40 mg/L may identify patients with IBS-C with a high specificity. In the IBS group, there was a strong negative correlation between abdominal pain severity and RvD1 concentration (r=-0.766, p=0.001). CONCLUSION This research demonstrates that patients with IBS-C have higher CRP and lower RvD1 concentrations than healthy controls. Both RvD1 and CRP concentrations predict the presence of IBS-C. Additionally, RvD1 concentrations decreased with the increase in abdominal pain severity. Further research works are needed for investigating the role of the RvD1 analogs in the treatment of IBS.
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Affiliation(s)
- Eylem Karatay
- Department of Gastroenterology, GOP Taksim Training and Research Hospital, İstanbul, Turkey
| | - Özlem Gül Utku
- Department of Gastroenterology, Kırıkkale University School of Medicine, Kırıkkale, Turkey
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The efficacy and safety of probiotics in patients with irritable bowel syndrome: Evidence based on 35 randomized controlled trials. Int J Surg 2020; 75:116-127. [DOI: 10.1016/j.ijsu.2020.01.142] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 01/11/2020] [Accepted: 01/27/2020] [Indexed: 12/11/2022]
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Zhang Y, Wu XX, Li S, Wu JF, Han S, Lin ZJ, Ding SZ, Gong WJ. Peroxiredoxin 1 as an inflammatory marker in diarrhea-predominant and postinfectious irritable bowel syndrome. Neurogastroenterol Motil 2020; 32:e13741. [PMID: 31613423 DOI: 10.1111/nmo.13741] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 09/12/2019] [Accepted: 09/18/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Low-grade inflammation occurs in some patients with irritable bowel syndrome (IBS). However, the exact inflammatory markers of IBS and the relationship of these markers with IBS subtypes and symptoms are poorly defined. Peroxiredoxin 1 (PRDX1) plays an important role in inflammatory responses, including intestinal inflammation. We investigated whether PRDX1 is associated with the diagnosis, subtypes, and symptom severity of IBS. METHODS A total of 177 IBS patients and 174 sex- and age-matched healthy controls (HCs) were recruited. The PRDX1 levels in the sera and colonic mucosa of the participants were detected by enzyme-linked immunosorbent assays and immunohistochemistry. The severity of IBS symptoms was assessed using the IBS Severity Scoring System (SSS) questionnaire. RESULTS The PRDX1 levels in the sera (F = 71.81, P < .001) and colonic mucosa (F = 5.359, P < .001) of postinfectious (PI-IBS) and diarrhea-predominant IBS (IBS-D) groups were significantly higher than those of the other three IBS subtypes and HC group. The PRDX1 level in the serum and colonic mucosa of IBS-D (serum, P < .01, mucosa, P < .001) and PI-IBS (serum, P < .05, mucosa, P < .001) groups with the most severe symptoms was significantly higher than that in the groups with mild and moderate symptoms. Correlation analysis revealed that in patients with IBS-D (P < .001) and PI-IBS (P < .05), the levels of PRDX1 and TNF-α in sera had a significant positive correlation with IBS-SSS. CONCLUSION Elevated PRDX1 in the serum and colon mucosa may be closely related to the progression of IBS (especially IBS-D and PI-IBS) and the expression of gastrointestinal symptoms.
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Affiliation(s)
- Yu Zhang
- School of Nursing, Yangzhou University, Yangzhou, China.,Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China
| | - Xia-Xin Wu
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Shuang Li
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Jin-Feng Wu
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Sen Han
- Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
| | - Zhi-Jie Lin
- Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
| | - Shi-Zhen Ding
- Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
| | - Wei-Juan Gong
- School of Nursing, Yangzhou University, Yangzhou, China.,Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
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Chey WD, Shah ED, DuPont HL. Mechanism of action and therapeutic benefit of rifaximin in patients with irritable bowel syndrome: a narrative review. Therap Adv Gastroenterol 2020; 13:1756284819897531. [PMID: 32047534 PMCID: PMC6984424 DOI: 10.1177/1756284819897531] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 12/02/2019] [Indexed: 02/04/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected. Small intestinal bacterial overgrowth (SIBO) is more common in patients with IBS than in healthy individuals, and eradication of SIBO with systemic antibiotics has decreased symptoms of IBS in some patients with IBS and SIBO. The nonsystemic (i.e. low oral bioavailability) antibiotic rifaximin is indicated in the United States and Canada for the treatment of adults with IBS with diarrhea (IBS-D). The efficacy and safety of 2-week single and repeat courses of rifaximin have been demonstrated in randomized, placebo-controlled studies of adults with IBS. Rifaximin is widely thought to exert its beneficial clinical effects in IBS-D through manipulation of the gut microbiota. However, current studies indicate that rifaximin induces only modest effects on the gut microbiota of patients with IBS-D, suggesting that the efficacy of rifaximin may involve other mechanisms. Indeed, preclinical data reveal a potential role for rifaximin in the modulation of inflammatory cytokines and intestinal permeability, but these two findings have not yet been examined in the context of clinical studies. The mechanism of action of rifaximin in IBS is likely multifactorial, and further study is needed.
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Affiliation(s)
- William D. Chey
- Department of Nutrition Sciences, Division of Gastroenterology, Michigan Medicine, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109-5362, USA
| | - Eric D. Shah
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Herbert L. DuPont
- Division of Epidemiology, Human Genetics and Environmental Sciences and Center for Infectious Diseases, University of Texas School of Public Health, Houston, TX, USA
- Mary W. Kelsey Chair in Medical Sciences, Division of Internal Medicine, University of Texas McGovern Medical School Houston, TX, USA
- Kelsey Research Foundation, Houston, TX, USA
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Rossi G, Gioacchini G, Pengo G, Suchodolski JS, Jergens AE, Allenspach K, Gavazza A, Scarpona S, Berardi S, Galosi L, Bassotti G, Cerquetella M. Enterocolic increase of cannabinoid receptor type 1 and type 2 and clinical improvement after probiotic administration in dogs with chronic signs of colonic dysmotility without mucosal inflammatory changes. Neurogastroenterol Motil 2020; 32:e13717. [PMID: 31495983 DOI: 10.1111/nmo.13717] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 08/20/2019] [Accepted: 08/20/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Colonic dysmotility in dogs can cause different GI signs. Sometimes, histology of enterocolic biopsies does not reveal inflammatory infiltrates or mucosal lesions that are typically associated with clinical disease activity. It is speculated that, similarly to humans, colonic dysmotility may be anxiety-based, although recent data demonstrate that irritable bowel syndrome (IBS) could result from acute infectious enteritis. Specific Lactobacillus spp. strains administered orally in humans induced the expression of μ-opioid and cannabinoid receptors in mucosal enterocytes, modulating intestinal morphine-like analgesic functions. We investigated the potential association of GI signs caused by colonic dysmotility and mucosal expression of cannabinoid receptors in intestinal epithelial cells and the number of mucosal mast cells. METHODS Ten to 15 endoscopic biopsies were collected from colonic mucosa of 20 dogs diagnosed with dysmotility disturbances before and after probiotic (Slab51 bacterial blend; Sivoy® ) administration (3-month period). Number and distribution of mast cells (MCs), and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated by immunohistochemistry and PCR. Results were compared to data obtained from five clinically healthy dogs (archive samples). KEY RESULTS Decreased numbers of MCs (P < .0001) and increased CB1- and CB2-positive epithelial cells (P < .0001) in diseased dogs were positively associated with post-treatment CCECAI scores (P < .0001). CONCLUSIONS AND INFERENCES Our results suggest that probiotic administration can reduce signs of colonic dysmotility, possibly due to microbiota modulation and epithelial cell receptor-mediated signaling in intestinal mucosa.
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Affiliation(s)
- Giacomo Rossi
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Giorgia Gioacchini
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy
| | | | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA
| | - Albert E Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Karin Allenspach
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Alessandra Gavazza
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Silvia Scarpona
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Sara Berardi
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Livio Galosi
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Gabrio Bassotti
- Gastroenterology and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Matteo Cerquetella
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
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García-Carrasco M, Mendoza-Pinto C, Munguía-Realpozo P, Méndez-Valderrabano F, Méndez Martínez S, Etchegaray Morales I, Montiel-Jarquín Á, López-Colombo A, Schmulson M. Functional gastrointestinal disorders in women with systemic lupus erythematosus: A case-control study. Neurogastroenterol Motil 2019; 31:e13693. [PMID: 31373090 DOI: 10.1111/nmo.13693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/15/2019] [Accepted: 07/20/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is an autoimmune disease with multisystemic involvement. Gastrointestinal (GI) manifestations are frequent but functional gastrointestinal disorders (FGIDs) have scarcely been studied in SLE. To determine the prevalence of FGIDs and their potential risk factors in SLE female patients vs controls. METHODS Systemic lupus erythematosus patients meeting the American College of Rheumatology (ACR) criteria and controls completed the Rome III questionnaire for FGIDs and a structured interview to assess sociodemographic, clinical, and treatment variables after excluding organic GI diseases. Logistic regression was used to determine risk factors (ie, alcohol drinking, medications) for FGIDs. KEY RESULTS Responders included 113 SLE patients and 122 age-matched controls. The presence of at least one FGIDs was higher in SLE (73.4%) vs controls (54.1%), P = .003. The most frequent FGIDs in SLE patients were nausea and vomiting disorders (NVD), belching disorders, globus, anorectal pain, functional heartburn (FH), and functional bloating (FB). After adjustment for confounding variables, SLE was associated with NVD (OR: 7.1, 95% CI: 2.7-19.1) globus (3.5, 1.3-9.3), anorectal pain (3.4, 1.4-8.4), and FH (2.5, 1.5-4.4). The simultaneous presence of >1 FGID was more common in SLE patients than controls (69.8% vs 31.8%). Glucocorticoids (5.2, 1.3-19.9) and non-steroidal anti-inflammatory drugs (NSAIDs; 3.0, 1.1-8.0) were associated with any FGID in SLE patients while alcohol drinking with gallbladder/sphincter of Oddi disorders 7.4 (1.1-47.3). CONCLUSIONS AND INFERENCES Functional gastrointestinal disorders are more frequent in SLE patients compared with controls. Medication that may alter gastrointestinal homeostasis, such as glucocorticoids and NSAIDs, are potential risk factors for FGIDs in SLE.
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Affiliation(s)
- Mario García-Carrasco
- Systemic Autoimmune Diseases Research Unit, Hospital de Especialidades, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México.,Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, IMSS, Puebla, México.,Immunology and Rheumatology, Medicine School, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | - Claudia Mendoza-Pinto
- Systemic Autoimmune Diseases Research Unit, Hospital de Especialidades, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México.,Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, IMSS, Puebla, México.,Immunology and Rheumatology, Medicine School, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | - Pamela Munguía-Realpozo
- Systemic Autoimmune Diseases Research Unit, Hospital de Especialidades, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México
| | - Fabiola Méndez-Valderrabano
- Systemic Autoimmune Diseases Research Unit, Hospital de Especialidades, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México
| | - Socorro Méndez Martínez
- Research in Health Coordination, Puebla Delegation, Instituto Mexicano del Seguro Social, Puebla, México
| | - Ivet Etchegaray Morales
- Immunology and Rheumatology, Medicine School, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | - Álvaro Montiel-Jarquín
- Division of Health Research, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México
| | - Aurelio López-Colombo
- State Research and Education Department, UMAE Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México
| | - Max Schmulson
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM)-Hospital General de México, Dr. Eduardo Liceaga., Mexico City, México
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Zhao Q, Yang WR, Wang XH, Li GQ, Xu LQ, Cui X, Liu Y, Zuo XL. Clostridium butyricum alleviates intestinal low-grade inflammation in TNBS-induced irritable bowel syndrome in mice by regulating functional status of lamina propria dendritic cells. World J Gastroenterol 2019; 25:5469-5482. [PMID: 31576093 PMCID: PMC6767978 DOI: 10.3748/wjg.v25.i36.5469] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/17/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gas-troenterological diseases characterized by abnormal visceral sensitivity and low-grade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1β, IL-6, and others) and express T cell immuno-globulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses.
AIM To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention.
METHODS An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrow-derived dendritic cells by in vitro experiments.
RESULTS The secretion of proinflammatory cytokines (IL-1β and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1β and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response.
CONCLUSION The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine.
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Affiliation(s)
- Qin Zhao
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
- Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China
| | - Wen-Rong Yang
- Department of Clinical Nutrition, Taian City Central Hospital, Taian 271000, Shandong Province, China
| | - Xiao-Hong Wang
- Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China
| | - Gai-Qin Li
- Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China
| | - Lei-Qi Xu
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Xiao Cui
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Yang Liu
- Department of Medicine, Beijing 316 Hospital, Beijing 100093, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
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A clinical model for identifying an inflammatory phenotype in mood disorders. J Psychiatr Res 2019; 113:148-158. [PMID: 30954775 DOI: 10.1016/j.jpsychires.2019.02.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 01/20/2019] [Accepted: 02/07/2019] [Indexed: 12/14/2022]
Abstract
Increasingly, clinical research has found inflammatory correlates of psychiatric disorders, particularly mood symptomatology. Biological measures may provide greater precision in many cases and may capture clinically-relevant inflammatory signposts, such as central obesity risk, inflammation-associated co-morbid medical conditions, or proinflammatory lifestyle choices. In order to expand understanding of the role of inflammation in mood disorders, we propose a more inclusive clinical model for capturing an inflammatory phenotype of depression by identifying clinically-relevant inflammatory phenotypes grounded in biology. Our model includes chronic conditions and lifestyle behaviors associated with clinically elevated inflammation in mood disorders. Elements of this "inflamed depression" model include: obesity, low HDL concentrations, elevated triglyceride concentrations, chronically elevated blood pressure, clinical diagnosis of hypothyroidism, migraines, rheumatoid arthritis, adult onset diabetes, inflammatory bowel diseases, inflammatory skin conditions, and lifestyle factors including smoking cigarettes and chronic stress.
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Gracie DJ, Hamlin PJ, Ford AC. The influence of the brain-gut axis in inflammatory bowel disease and possible implications for treatment. Lancet Gastroenterol Hepatol 2019; 4:632-642. [PMID: 31122802 DOI: 10.1016/s2468-1253(19)30089-5] [Citation(s) in RCA: 206] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/05/2019] [Accepted: 03/06/2019] [Indexed: 12/11/2022]
Abstract
Brain-gut interactions affect psychological wellbeing and symptom reporting in functional gastrointestinal disorders; the presence of anxiety or depression is associated with the development of new-onset gastrointestinal symptoms, and the presence of gastrointestinal symptoms is associated with the development of psychological disorders de novo. In inflammatory bowel diseases (IBD), the reporting of irritable bowel syndrome (IBS)-type symptoms by patients with quiescent disease is common, and is associated with psychological disorders, impaired quality of life, and increased health-care use. In IBD, data from observational studies suggest that psychological disorders might be associated with relapse of disease activity, and that inflammatory activity is associated with the development of new psychological disorders, as has been described for functional gastrointestinal disorders such as IBS and functional dyspepsia. The brain-gut axis provides the physiological link between the CNS and gastrointestinal tract that might facilitate these relationships. In IBS, treatments targeting disordered brain-gut axis activity, including psychological therapies and antidepressants, might lead to improved symptoms and quality of life. However, in IBD, the benefit of these treatments is less certain because of a scarcity of interventional studies. Despite the scarcity of trials, observational data suggest that the effect of disordered brain-gut axis activity in IBD is substantial, and scope remains for further well designed trials of psychological therapies and antidepressants, particularly in the subset of patients who have coexistent psychological disorders, or in those who report IBS-type symptoms. Integrating these treatments into a biopsychosocial model of care has the potential to improve both psychological wellbeing and quality of life in some patients with IBD, reducing health-care use and altering the natural history of disease.
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Affiliation(s)
- David J Gracie
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.
| | - P John Hamlin
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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Li Y, Yang T, Yao Q, Li S, Fang E, Li Y, Liu C, Li W. Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation-induced IBS-like rats. Neurogastroenterol Motil 2019; 31:e13556. [PMID: 30740845 DOI: 10.1111/nmo.13556] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 11/23/2018] [Accepted: 12/27/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Intestinal barrier dysfunction is a key etiologic factor of irritable bowel syndrome (IBS). Metformin improves intestinal barrier function, although the underlying mechanism has yet to be fully explained. This study evaluates the protective effect of metformin on colonic barrier integrity and explores the underlying cellular mechanisms. METHODS IBS-like rats were induced by maternal separation. Metformin was administered daily by gavage at 08:30, and rat pups were then separated from their mother. Visceral hyperalgesia and depression-like behaviors were evaluated by colorectal distension, sucrose preference tests, and forced swimming tests. Intestinal integrity was analyzed using sugar probes and transmission electron microscopy. Inflammatory factors and the levels of corticotropin-releasing factor were assessed by PCR and ELISA. The number of mast cells was evaluated by toluidine blue staining. Protein expression and localization were determined using Western blot and immunochemistry. KEY RESULTS Metformin pretreatment (a) reduced visceral hypersensitivity to colorectal distension, immobility time and enhanced sucrose consumption; (b) decreased urine lactulose/mannitol ratio and sucralose output; (c) inhibited the dilation of tight junction and prevented claudin-4 translocation; (d) inhibited mast cell activation and downregulated the expression of IL-6, IL-18, tryptase, PAR-2, and ERK activation; (e) inhibited claudin-4 phosphorylation at serine sites and interactions between clau-4 and ZO-1. CONCLUSIONS & INFERENCES Metformin may block mast cell activation to reduce PAR-2 expression and subsequently inhibit ERK activation and clau-4 phosphorylation at serine sites to normalize the interaction of clau-4 and ZO-1 and clau-4 distribution. Metformin may be clinically beneficial for patients with IBS or IBS-like symptoms.
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Affiliation(s)
- Yong Li
- Laboratory of Neuronal Network and Systems Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.,Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China
| | - Tingting Yang
- Laboratory of Neuronal Network and Systems Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qing Yao
- Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China
| | - Songsong Li
- Xianning Institute for Drug Control, Xianning, China
| | - En Fang
- Xianning Institute for Drug Control, Xianning, China
| | - Yankun Li
- College of Pharmacy, Hubei University of Science and Technology, Xianning, China
| | - Chao Liu
- Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China
| | - Weimin Li
- Laboratory of Neuronal Network and Systems Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
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