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Manipis K, Cronin P, Street D, Church J, Viney R, Goodall S. Examination of Methods to Estimate Productivity Losses in an Economic Evaluation: Using Foodborne Illness as a Case Study. PHARMACOECONOMICS 2025; 43:453-467. [PMID: 39754692 DOI: 10.1007/s40273-024-01458-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/21/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND Cost-utility analyses commonly use two primary methods to value productivity: the human capital approach (HCA) and the friction cost approach (FCA). Another less frequently used method is the willingness-to-pay (WTP) approach, which estimates the monetary value individuals assign to avoiding an illness. In the context of foodborne illnesses (FBI), productivity loss represents one of the most significant economic impacts, particularly in developed nations. These losses arise from factors such as missed workdays, reduced workplace efficiency due to illness, and long-term health complications that can limit an individual's ability to work. As a result, accurately quantifying productivity loss is critical in understanding the broader economic burden of FBI. AIM Our aim was to compare the impact of valuation methods used to measure productivity loss in an economic evaluation, using a hypothetical intervention for FBI caused by campylobacter as a case study. Cost effectiveness from three perspectives is examined: health care system, employee, and employer. METHOD A Markov model with a 10-year time horizon was developed to evaluate the morbidity and productivity impacts of FBI caused by campylobacter. The model included four health states: 'healthy', 'acute gastroenteritis', 'irritable bowel syndrome and being unable to work some of the time', and 'irritable bowel syndrome and unable to work'. Five approaches to valuing productivity loss were compared: model 1 (cost-utility analysis), model 2 (HCA), model 3 (FCA), model 4 (FCA+WTP to avoid illness with paid sick leave), and model 5 (WTP to avoid illness without paid sick leave). Health outcomes and costs were discounted using a 5% discount rate. Costs were reported in 2024 Australian dollars ($AUD). RESULTS Model 1, which did not include productivity losses, yielded the highest incremental cost-effectiveness ratio (ICER) at $56,467 per quality-adjusted life-year (QALY) gained. The inclusion of productivity costs (models 2-5) significantly increased the total costs in both arms of the models but led to a marked reduction in the ICERs. For example, model 2 (HCA) resulted in an ICER of $11,174/QALY gained, whereas model 3 (FCA) resulted in $21,136/QALY gained. Models 4 and 5, which included WTP approaches, had ICERs of $19,661/QALY gained and $24,773/QALY gained, respectively. CONCLUSION These findings underscore the significant impact of different modelling approaches to productivity loss on ICER estimates and consequently the decision to adopt a new policy or intervention. The choice of perspective in the analysis is critical, as it determines how the short-term and long-term productivity losses are accounted for and valued. This highlights the importance of carefully selecting and justifying the perspective and valuation methods used in economic evaluations to ensure informed and balanced policy decisions.
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Affiliation(s)
- Kathleen Manipis
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.
| | - Paula Cronin
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia
| | - Deborah Street
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia
| | - Jody Church
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia
| | - Rosalie Viney
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia
| | - Stephen Goodall
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia
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Zhang D, Stein R, Lu Y, Zhou T, Lei Y, Li L, Chen J, Arnold J, Becich MJ, Chrischilles EA, Chuang CH, Christakis DA, Fort D, Geary CR, Hornig M, Kaushal R, Liebovitz DM, Mosa ASM, Morizono H, Mirhaji P, Dotson JL, Pulgarin C, Sills MR, Suresh S, Williams DA, Baldassano RN, Forrest CB, Chen Y. Pediatric Gastrointestinal Tract Outcomes During the Postacute Phase of COVID-19. JAMA Netw Open 2025; 8:e2458366. [PMID: 39918822 PMCID: PMC11806396 DOI: 10.1001/jamanetworkopen.2024.58366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 12/03/2024] [Indexed: 02/09/2025] Open
Abstract
Importance The profile of gastrointestinal (GI) tract outcomes associated with the postacute and chronic phases of COVID-19 in children and adolescents remains unclear. Objective To investigate the risks of GI tract symptoms and disorders during the postacute (28-179 days after documented SARS-CoV-2 infection) and the chronic (180-729 days after documented SARS-CoV-2 infection) phases of COVID-19 in the pediatric population. Design, Setting, and Participants This retrospective cohort study was performed from March 1, 2020, to September 1, 2023, at 29 US health care institutions. Participants included pediatric patients 18 years or younger with at least 6 months of follow-up. Data analysis was conducted from November 1, 2023, to February 29, 2024. Exposures Presence or absence of documented SARS-CoV-2 infection. Documented SARS-CoV-2 infection included positive results of polymerase chain reaction analysis, serological tests, or antigen tests for SARS-CoV-2 or diagnosis codes for COVID-19 and postacute sequelae of SARS-CoV-2. Main Outcomes and Measures GI tract symptoms and disorders were identified by diagnostic codes in the postacute and chronic phases following documented SARS-CoV-2 infection. The adjusted risk ratios (ARRs) and 95% CI were determined using a stratified Poisson regression model, with strata computed based on the propensity score. Results The cohort consisted of 1 576 933 pediatric patients (mean [SD] age, 7.3 [5.7] years; 820 315 [52.0%] male). Of these, 413 455 patients had documented SARS-CoV-2 infection and 1 163 478 did not; 157 800 (13.6%) of those without documented SARS-CoV-2 infection had a complex chronic condition per the Pediatric Medical Complexity Algorithm. Patients with a documented SARS-CoV-2 infection had an increased risk of developing at least 1 GI tract symptom or disorder in both the postacute (8.64% vs 6.85%; ARR, 1.25; 95% CI, 1.24-1.27) and chronic (12.60% vs 9.47%; ARR, 1.28; 95% CI, 1.26-1.30) phases compared with patients without a documented infection. Specifically, the risk of abdominal pain was higher in COVID-19-positive patients during the postacute (2.54% vs 2.06%; ARR, 1.14; 95% CI, 1.11-1.17) and chronic (4.57% vs 3.40%; ARR, 1.24; 95% CI, 1.22-1.27) phases. Conclusions and Relevance In this cohort study, the increased risk of GI tract symptoms and disorders was associated with the documented SARS-CoV-2 infection in children or adolescents during the postacute or chronic phase. Clinicians should note that lingering GI tract symptoms may be more common in children after documented SARS-CoV-2 infection than in those without documented infection.
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Affiliation(s)
- Dazheng Zhang
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Ronen Stein
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Yiwen Lu
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia
| | - Ting Zhou
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Yuqing Lei
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Lu Li
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia
| | - Jiajie Chen
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Jonathan Arnold
- Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Michael J. Becich
- Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Cynthia H. Chuang
- Division of General Internal Medicine, Penn State College of Medicine, Hershey, Pennsylvania
| | - Dimitri A. Christakis
- Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, Seattle, Washington
| | - Daniel Fort
- Ochsner Center for Outcomes Research, Ochsner Health, New Orleans, Louisiana
| | - Carol R. Geary
- College of Medicine, University of Nebraska Medical Center, Omaha
| | - Mady Hornig
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
| | - Rainu Kaushal
- Department of Population Health Sciences, Weill Cornell Medical College, New York, New York
| | - David M. Liebovitz
- Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Abu S. M. Mosa
- Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri School of Medicine, Columbia
| | - Hiroki Morizono
- Center for Genetic Medicine Research, Children’s National Hospital, Washington, DC
| | - Parsa Mirhaji
- Institute for Clinical Translational Research, Albert Einstein College of Medicine, New York, New York
| | - Jennifer L. Dotson
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock
| | - Claudia Pulgarin
- Department of Population Health, New York University Grossman School of Medicine, New York, New York
| | - Marion R. Sills
- Department of Research, OCHIN, Inc, Portland, Oregon
- Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora
| | - Srinivasan Suresh
- Division of Health Informatics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Division of Emergency Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Robert N. Baldassano
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Christopher B. Forrest
- Applied Clinical Research Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Yong Chen
- The Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia
- Penn Institute for Biomedical Informatics, Philadelphia, Pennsylvania
- Leonard Davis Institute of Health Economics, Philadelphia, Pennsylvania
- Penn Medicine Center for Evidence-based Practice, Philadelphia, Pennsylvania
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Lee JG, Lee SP, sup, 2, 3, sup, Jang HJ, Kae SH, Shin WG, Seo SI, Lim H, Kang HS, Soh JS, Bang CS, Yang YJ, Baik GH, Kim JB, Kim YJ, Oh CK, Hallym Gastrointestinal Study Group. Incidence and Clinical Course of Post-infectious Irritable Bowel Syndrome in Patients Admitted to University Hospitals: 1-year Prospective Follow-up Study. J Neurogastroenterol Motil 2025; 31:110-118. [PMID: 39694067 PMCID: PMC11735206 DOI: 10.5056/jnm24018] [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: 01/28/2024] [Revised: 03/26/2024] [Accepted: 04/10/2024] [Indexed: 12/20/2024] Open
Abstract
Background/Aims Post-infectious irritable bowel syndrome (PI-IBS) is characterized by chronic gastrointestinal symptoms that arise following an episode of infectious enteritis. The incidence rates vary, ranging from 5% to 32% and the risk factors are not well known. We aim to investigate the incidence and risk factors of PI-IBS in enteritis patients admitted to university hospitals in Korea. Methods This multi-center prospective study was conducted in patients hospitalized for infectious enteritis. Each patient underwent 1 outpatient visit and 3 telephone surveys during the first year after discharge to determine if PI-IBS occurred within the follow-up period. Results In the 3-month survey, 7 out of 354 patients (2%) were diagnosed with PI-IBS, and after 1 year, only 1 patient met the criteria for IBS. No statistically significant difference was found between the PI-IBS group and the non-PI-IBS group in terms of age, sex, underlying diseases, medication history, gastrointestinal symptoms, enteritis location, causative strain, hospitalization and treatment periods, and laboratory findings. Female sex (P = 0.003), enteropathogenic Escherichia coli (EPEC) infection (P = 0.044), and a longer total treatment period (P = 0.018) were independent risk factors for diarrhea lasting ≥ 3 months after enteritis. Conclusions The incidence of PI-IBS in Korea was relatively low, and most cases improved over time. No risk factors associated with the development of PI-IBS were found. However, persistent diarrhea after enteritis was associated with female sex, EPEC infection, and severe or long-lasting enteritis. IBS symptoms may persist after severe enteritis but usually improve with time.
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Affiliation(s)
- Jae Gon Lee
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Sang Pyo Lee
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - sup
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - 2
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - 3
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - sup
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Hyun Joo Jang
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Sea Hyub Kae
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Woon Geon Shin
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Seung In Seo
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hyun Lim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Ho Suk Kang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jae Seung Soh
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Chang Seok Bang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Young Joo Yang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ho Baik
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Jin Bae Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Yu Jin Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Chang Kyo Oh
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
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Haedrich J, Huber R. Crohn's disease, irritable bowel syndrome, and chronic fatigue: the importance of communication and symptom management-a case report. J Med Case Rep 2025; 19:9. [PMID: 39789666 PMCID: PMC11721286 DOI: 10.1186/s13256-024-05010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/12/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Crohn's disease and irritable bowel syndrome may both cause abdominal pain and diarrhea. Irritable bowel syndrome not only is an important differential diagnosis for Crohn's disease but also occurs in one out of three patients with Crohn's disease in remission in parallel. If not adequately diagnosed and treated, additional functional symptoms such as fatigue and/or muscle pain may develop, indicating a more severe course. CASE PRESENTATION A 64-year-old Caucasian male with long-standing, widely inactive Crohn's disease presented with persistent diarrhea, bloating, abdominal pain, general fatigue, unexplained hip pain, and frequent shivering with cold extremities, which had worsened following a gastrointestinal infection and psychological stress. A plausible explanation of his symptoms, based on an understanding of mind-body interactions, the autonomic nervous system, and temperature regulation, combined with symptom relief, was associated with rapid and sustainable improvement. After 2.5 years of follow-up, the patient is almost symptom-free. CONCLUSIONS This case report exemplifies the interrelation between organic (Crohn's disease) and functional diseases (irritable bowel syndrome, chronic fatigue syndrome, and somatoform pain). It further demonstrates that these connections may be overlooked in daily practice and that providing a plausible explanation in combination with symptom relief may be important for patients with functional syndromes.
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Affiliation(s)
- Johannes Haedrich
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany
| | - Roman Huber
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany.
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Lu S, Chen Y, Guo H, Liu Z, Du Y, Duan L. Differences in clinical manifestations and the fecal microbiome between irritable bowel syndrome and small intestinal bacterial overgrowth. Dig Liver Dis 2024; 56:2027-2037. [PMID: 39043536 DOI: 10.1016/j.dld.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 07/04/2024] [Accepted: 07/06/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share similar abdominal symptoms; however, their differentiation remains controversial. AIMS To illustrate the differences between the two conditions. METHODS Patients and healthy controls completed questionnaires and provided stool samples for analysis. RESULTS IBS presented with the most severe symptoms and was specifically characterized by intense abdominal pain and frequent episodes of diarrhea. Patients with IBS displayed more dysregulated taxonomy within the fecal microbiota than SIBO. Opportunistic pathogens, including Lachnoclostridium, Escherichia-Shigella, and Enterobacter were enriched in the IBS group which contributed to increased bacterial pathogenicity and positively correlated with abdominal pain and bloating, meanwhile, Lachnoclostridium and Escherichia-Shigella were found to be associated with metabolites affiliated to bile acids, alcohols and derivatives. Bacteria enriched in SIBO group correlated with constipation. The bacterial co-occurrence network within the SIBO group was the most intricate. Ruminococcaceae Group were defined as core bacteria in SIBO. Differential metabolites affiliated to androstane steroids and phenylacetic acids were associated with core bacteria. CONCLUSIONS Our study elucidates the differences between IBS and SIBO in terms of symptoms, microbiota and functions, which provides insights into a better understanding of both diseases and evidence for different treatment strategies.
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Affiliation(s)
- Siqi Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yuzhu Chen
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Huaizhu Guo
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Zuojing Liu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yanlin Du
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
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Jiang S, Pei L, Chen L, Sun J, Song Y. Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota. Microb Physiol 2024; 34:255-263. [PMID: 39396501 DOI: 10.1159/000541888] [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: 11/09/2023] [Accepted: 10/07/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. METHODS 2,4,6-trinitrobenzene sulfonic acid was used to induce visceral hypersensitivity in PI-IBS mice. Intestinal visceral sensitivity was assessed by using the abdominal withdrawal reflex (colorectal distention). 16S ribosomal RNA sequencing profiles the gut microbiome community. RESULTS GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. CONCLUSION EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.
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Affiliation(s)
- Shiyuan Jiang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China,
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China,
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China,
| | - Lixia Pei
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianhua Sun
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yafang Song
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China
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Lee K, Park J, Lee J, Lee M, Kim HJ, Son Y, Rhee SY, Smith L, Rahmati M, Kang J, Lee H, Ha Y, Yon DK. Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK. Clin Mol Hepatol 2024; 30:943-958. [PMID: 39205608 PMCID: PMC11540398 DOI: 10.3350/cmh.2024.0203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND/AIMS Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities. METHODS We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls. RESULTS The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08-1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09-1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01-1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort. CONCLUSION The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.
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Affiliation(s)
- Kwanjoo Lee
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jaeyu Park
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Regulatory Science, Kyung Hee University, Seoul, Korea
| | - Jinseok Lee
- Department of Biomedical Engineering, Kyung Hee University, Yongin, Korea
| | - Myeongcheol Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Regulatory Science, Kyung Hee University, Seoul, Korea
| | - Hyeon Jin Kim
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Regulatory Science, Kyung Hee University, Seoul, Korea
| | - Yejun Son
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Regulatory Science, Kyung Hee University, Seoul, Korea
| | - Sang Youl Rhee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Lee Smith
- Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Masoud Rahmati
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran
- Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran
- CEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hopitaux de Marseille, Aix-Marseille University, Marseille, France
| | - Jiseung Kang
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
- Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
| | - Hayeon Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Biomedical Engineering, Kyung Hee University, Yongin, Korea
| | - Yeonjung Ha
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Korea
- Department of Regulatory Science, Kyung Hee University, Seoul, Korea
- Department of Pediatrics, Kyung Hee University College of Medicine, Seoul, Korea
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Leite G, Rezaie A, Morales W, Weitsman S, de Freitas Germano J, Barlow GM, Parodi G, Pimentel ML, Villanueva-Millan MJ, Sanchez M, Ayyad S, Mathur R, Pimentel M. Low dose rifaximin combined with N-acetylcysteine is superior to rifaximin alone in a rat model of IBS-D: a randomized trial. Sci Rep 2024; 14:18140. [PMID: 39103611 PMCID: PMC11300865 DOI: 10.1038/s41598-024-69162-4] [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: 05/31/2024] [Accepted: 08/01/2024] [Indexed: 08/07/2024] Open
Abstract
Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.
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Affiliation(s)
- Gabriela Leite
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Ali Rezaie
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Walter Morales
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Stacy Weitsman
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | | | - Gillian M Barlow
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Gonzalo Parodi
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Maya L Pimentel
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | | | - Maritza Sanchez
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Sarah Ayyad
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Ruchi Mathur
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Mark Pimentel
- Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA.
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA.
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9
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Varma S, Sullivan K, DiCarlo J, Coromilas A, Staller K, Dougan M. The Development of Persistent Gastrointestinal Symptoms in Patients With Melanoma Who Have Had an Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity. Clin Transl Gastroenterol 2024; 15:e00746. [PMID: 38995215 PMCID: PMC11346846 DOI: 10.14309/ctg.0000000000000746] [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: 04/15/2024] [Accepted: 06/27/2024] [Indexed: 07/13/2024] Open
Abstract
INTRODUCTION Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE. METHODS This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms. RESULTS One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23). DISCUSSION In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.
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Affiliation(s)
- Sanskriti Varma
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Center for Neurointestinal Health, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Keri Sullivan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Jamie DiCarlo
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Alexandra Coromilas
- Department of Dermatology, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, New York City, New York, USA
| | - Kyle Staller
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Center for Neurointestinal Health, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Michael Dougan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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10
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Zhang D, Stein R, Lu Y, Zhou T, Lei Y, Li L, Chen J, Arnold J, Becich MJ, Chrischilles EA, Chuang CH, Christakis DA, Fort D, Geary CR, Hornig M, Kaushal R, Liebovitz DM, Mosa ASM, Morizono H, Mirhaji P, Dotson JL, Pulgarin C, Sills MR, Suresh S, Williams DA, Baldassano RN, Forrest CB, Chen Y. Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19: Findings from RECOVER Initiative from 29 Hospitals in the US. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.05.21.24307699. [PMID: 38826331 PMCID: PMC11142297 DOI: 10.1101/2024.05.21.24307699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2024]
Abstract
Importance The profile of gastrointestinal (GI) outcomes that may affect children in post-acute and chronic phases of COVID-19 remains unclear. Objective To investigate the risks of GI symptoms and disorders during the post-acute phase (28 days to 179 days after SARS-CoV-2 infection) and the chronic phase (180 days to 729 days after SARS-CoV-2 infection) in the pediatric population. Design We used a retrospective cohort design from March 2020 to Sept 2023. Setting twenty-nine healthcare institutions. Participants A total of 413,455 patients aged not above 18 with SARS-CoV-2 infection and 1,163,478 patients without SARS-CoV-2 infection. Exposures Documented SARS-CoV-2 infection, including positive polymerase chain reaction (PCR), serology, or antigen tests for SARS-CoV-2, or diagnoses of COVID-19 and COVID-related conditions. Main Outcomes and Measures Prespecified GI symptoms and disorders during two intervals: post-acute phase and chronic phase following the documented SARS-CoV-2 infection. The adjusted risk ratio (aRR) was determined using a stratified Poisson regression model, with strata computed based on the propensity score. Results Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). Conclusions and Relevance In the post-acute phase or chronic phase of COVID-19, the risk of GI symptoms and disorders was increased for COVID-positive patients in the pediatric population.
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Affiliation(s)
- Dazheng Zhang
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Ronen Stein
- Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Yiwen Lu
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States
| | - Ting Zhou
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Yuqing Lei
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Lu Li
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States
| | - Jiajie Chen
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Jonathan Arnold
- Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Michael J. Becich
- Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Elizabeth A. Chrischilles
- Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, United States
| | - Cynthia H. Chuang
- Division of General Internal Medicine, Penn State College of Medicine, Hershey, PA, United States
| | - Dimitri A Christakis
- Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, Seattle, WA, United States
| | - Daniel Fort
- Ochsner Center for Outcomes Research, Ochsner Health, New Orleans, LA, United States
| | - Carol R. Geary
- College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Mady Hornig
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States
| | - Rainu Kaushal
- Department of Population Health Sciences, Weill Cornell Medical College, New York, NY, United States
| | - David M. Liebovitz
- Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Abu Saleh Mohammad Mosa
- Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri School of Medicine, Columbia, MO, United States
| | - Hiroki Morizono
- Center for Genetic Medicine Research, Children’s National Hospital, Washington, DC, United States
| | - Parsa Mirhaji
- Institute for Clinical Translational Research, Albert Einstein College of Medicine, New York, NY, United States
| | - Jennifer L. Dotson
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Claudia Pulgarin
- Department of Population Health, New York University Grossman School of Medicine, New York, NY, United States
| | - Marion R. Sills
- Department of Research, OCHIN, Inc., Portland, OR, United States
- University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Srinivasan Suresh
- Divisions of Health Informatics & Emergency Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
| | - David A. Williams
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States
| | - Robert N. Baldassano
- Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Christopher B. Forrest
- Applied Clinical Research Center, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
| | - Yong Chen
- The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, United States
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States
- Penn Institute for Biomedical Informatics (IBI), Philadelphia, PA, United States
- Leonard Davis Institute of Health Economics, Philadelphia, PA, United States
- Penn Medicine Center for Evidence-based Practice (CEP), Philadelphia, PA, United States
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11
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Zhang P, Ma S, Guo R, Li L, Guo X, Chang D, Li S, Zhang H, Fu C, Yang L, Zhang Y, Jiang J, Wang T, Wang J, Shi H. Metagenomic analysis of the gut virome in patients with irritable bowel syndrome. J Med Virol 2024; 96:e29802. [PMID: 39023095 DOI: 10.1002/jmv.29802] [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: 11/16/2023] [Revised: 07/02/2024] [Accepted: 07/04/2024] [Indexed: 07/20/2024]
Abstract
Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.
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Affiliation(s)
- Pan Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Shiyang Ma
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | | | - Lu Li
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Xiaoyan Guo
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Danyan Chang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | | | - Huan Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Cui Fu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Longbao Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Yue Zhang
- Puensum Genetech Institute, Wuhan, China
| | - Jiong Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Ting Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Jinhai Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
| | - Haitao Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Shaanxi, China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Shaanxi, China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, PR China
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12
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Afshari A, Rezaee R, Shakeri G. Foodborne pathogens and their association with well-known enteric infections and emerging non-communicable disorders. CABI REVIEWS 2024. [DOI: 10.1079/cabireviews.2024.0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Abstract
Annually, numerous new cases of communicable and non-communicable diseases are diagnosed, and consumption of food/water contaminated with different levels of microbial and chemical agents is responsible for a considerable portion of this burden. Generally, acute foodborne diseases are readily identified, while chronic deleterious effects are often neglected and rarely blamed for health consequences. The present work narrates a journey from consuming foods containing bacteria/bacterial toxins to developing chronic diseases, making humans more susceptible to emerging diseases. We aim to shed light on the chronic effects of foodborne diseases, particularly gastrointestinal disorders (GIDs) and inflammatory bowel diseases (IBDs), which are common chronic symptoms of most foodborne diseases.
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Affiliation(s)
- Asma Afshari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ramin Rezaee
- Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Golshan Shakeri
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- The German Federal Institute for Risk Assessment, Diedersdorfer Weg 1, D-12277 Berlin, Germany
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13
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Wang YN, Zhou LY, Huang YH, Jiang M, Dai C. The incidence and predisposing factors for irritable bowel syndrome following COVID-19: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:168-176. [PMID: 38047738 DOI: 10.1097/meg.0000000000002688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder. Several studies have analyzed the long-term GI symptoms and IBS following coronavirus disease 2019 (COVID-19). The purpose of this study is to evaluate the incidence and predisposing factors for IBS following COVID-19 by a systematic review and meta-analysis. METHODS Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled incidence rate of IBS following COVID-19 and the pooled relative risk (RR) for IBS in the COVID-19 group compared to the non-COVID-19 group. Secondary outcomes were the pooled RR and the standardized mean difference (SMD) for predisposing factors in the IBS group compared to the non-IBS group. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. RESULTS Ten studies were included in this study. The pooled incidence rate of IBS in COVID-19 patients was 12%. The pooled incidence rate of IBS-D, IBS-C and IBS-M was 5%, 2% and 1%. The pooled incidence rate of IBS in 6 and 12 months was 10% and 3%. The pooled RR for IBS in COVID-19 patients was 1.23 [95% confidence interval (CI) = 0.50-3.01] compared to non-COVID-19 patients. The pooled RR or SMD for mild, moderate, and severe disease activity, procalcitonin (PCT), depression or anxiety in IBS patients following COVID-19 was 0.94 (95% CI = 0.74-1.21), 1.19 (95% CI = 0.65-2.21), 1.30 (95% CI = 0.63-2.66), 6.73 (95% CI = 6.08-7.38) and 3.21 (95% CI = 1.79-5.75). CONCLUSION The incidence of IBS following COVID-19 was 12%. But it was not higher than the general population. We also found some predisposing factors for IBS including depression or anxiety, PCT.
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Affiliation(s)
- Yi-Nuo Wang
- Department of Gastroenterology, First Hospital of China Medical University, Shenyang, China
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14
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Kraimi N, Ross T, Pujo J, De Palma G. The gut microbiome in disorders of gut-brain interaction. Gut Microbes 2024; 16:2360233. [PMID: 38949979 PMCID: PMC11218806 DOI: 10.1080/19490976.2024.2360233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 05/21/2024] [Indexed: 07/03/2024] Open
Abstract
Functional gastrointestinal disorders (FGIDs), chronic disorders characterized by either abdominal pain, altered intestinal motility, or their combination, have a worldwide prevalence of more than 40% and impose a high socioeconomic burden with a significant decline in quality of life. Recently, FGIDs have been reclassified as disorders of gut-brain interaction (DGBI), reflecting the key role of the gut-brain bidirectional communication in these disorders and their impact on psychological comorbidities. Although, during the past decades, the field of DGBIs has advanced significantly, the molecular mechanisms underlying DGBIs pathogenesis and pathophysiology, and the role of the gut microbiome in these processes are not fully understood. This review aims to discuss the latest body of literature on the complex microbiota-gut-brain interactions and their implications in the pathogenesis of DGBIs. A better understanding of the existing communication pathways between the gut microbiome and the brain holds promise in developing effective therapeutic interventions for DGBIs.
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Affiliation(s)
- Narjis Kraimi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Taylor Ross
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Julien Pujo
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
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15
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Orock A, Johnson A, Mohammadi E, Greenwood-Van Meerveld B. Environmental enrichment reverses stress-induced changes in the brain-gut axis to ameliorate chronic visceral and somatic hypersensitivity. Neurobiol Stress 2024; 28:100590. [PMID: 38075024 PMCID: PMC10698671 DOI: 10.1016/j.ynstr.2023.100590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/02/2023] [Accepted: 11/12/2023] [Indexed: 02/12/2024] Open
Abstract
Introduction Behavioral therapies, including cognitive behavioral therapy, hypnotherapy and stress management activities, have emerged as effective treatments for irritable bowel syndrome (IBS), a female predominant disorder of the brain-gut axis. IBS, affecting over 10% of the global population, typically presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While the mechanisms underlying how behavioral therapies treat IBS are still elusive, we had previously shown that chronic stress alters gene expression in brain regions critical for stress processing and nociception. We found that exposure to an enriched environment (EE), the rodent analogue of behavioral therapies, prior to and during the stressor was sufficient to prevent stress-induced changes in glucocorticoid receptor (GR) expression in the central nucleus of the amygdala (CeA) and hippocampus. Pre-exposure to EE also inhibited stress-induced increased colonic permeability and was able to block the induction of stress-induced visceral and somatic hypersensitivity. However, it remains unknown if EE can reverse chronic viscerosomatic hypersensitivity that persists following exposure to stress. We hypothesized that EE after chronic stress would be sufficient to reverse stress-induced changes in i) GR expression in the CeA and hippocampus, ii) ameliorate stress-induced colonic hyperpermeability and iii) restore normal visceral and somatic sensitivity in male and female rats. Methods Male and female rats were exposed to daily water avoidance stress (WAS). After confirming the rats had developed visceral hypersensitivity, 50% of the animals were housed in EE for 2 weeks while the other 50% remained in standard housing (SH). At the end of this period, we assessed visceral and somatic sensitivity. We also collected colon tissue to measure colonic permeability. Micro-punches of tissue from the CeA and hippocampus were isolated to measure GR expression. Control animals not exposed to WAS were kept in SH for the duration of the study (n = 8 per group). Results In both male and female rats, EE reversed stress-induced visceral (p < 0.001) and somatic (p < 0.01) hypersensitivity when compared to WAS animals housed in SH to levels comparable to control animals. EE exposure also reversed changes in GR expression in both the hippocampus (p < 0.01) and CeA (p < 0.01), normalizing GR expression to control levels. EE exposure ameliorated stress-induced colonic hyperpermeability in both male (p < 0.01) and female (p < 0.01) rats compared to WAS rats in SH. Conclusion Our findings suggest that behavioral therapies are viable therapeutic options for IBS as they can counter the stress-induced pathophysiology underlying IBS symptoms including visceral hypersensitivity, increased colonic permeability and altered gene expression.
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Affiliation(s)
- A. Orock
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - A.C. Johnson
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Veterans Affairs Health Care System, Oklahoma City, OK, USA
| | - E. Mohammadi
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - B. Greenwood-Van Meerveld
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Veterans Affairs Health Care System, Oklahoma City, OK, USA
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Yau YK, Su Q, Xu Z, Tang W, Ching JYL, Mak JWY, Cheung CP, Fung M, Ip M, Chan PKS, Wu JCY, Chan FKL, Ng SC. Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 2023; 58:795-804. [PMID: 37667968 DOI: 10.1111/apt.17703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/11/2023] [Accepted: 08/23/2023] [Indexed: 09/06/2023]
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS). AIM We performed a randomised trial to assess the efficacy of FMT in patients with IBS. METHODS We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT. RESULTS At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT. CONCLUSION FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).
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Affiliation(s)
- Yuk Kam Yau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Qi Su
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zhilu Xu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Whitney Tang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
| | - Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chun Pan Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Matthew Fung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Margaret Ip
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Paul Kay Sheung Chan
- Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Justin Che Yuen Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Francis Ka Leung Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Microbiota I-Center (MagIC), Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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Napolitano M, Fasulo E, Ungaro F, Massimino L, Sinagra E, Danese S, Mandarino FV. Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications. Microorganisms 2023; 11:2369. [PMID: 37894027 PMCID: PMC10609453 DOI: 10.3390/microorganisms11102369] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/29/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.
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Affiliation(s)
- Maria Napolitano
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Ernesto Fasulo
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
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Lupu VV, Ghiciuc CM, Stefanescu G, Mihai CM, Popp A, Sasaran MO, Bozomitu L, Starcea IM, Adam Raileanu A, Lupu A. Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review. World J Gastroenterol 2023; 29:3241-3256. [PMID: 37377581 PMCID: PMC10292139 DOI: 10.3748/wjg.v29.i21.3241] [Citation(s) in RCA: 15] [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: 02/16/2023] [Revised: 04/04/2023] [Accepted: 05/08/2023] [Indexed: 06/01/2023] Open
Abstract
Post-infectious irritable bowel syndrome (PI-IBS) is a particular type of IBS, with symptom onset after an acute episode of infectious gastroenteritis. Despite infectious disease resolution and clearance of the inciting pathogen agent, 10% of patients will develop PI-IBS. In susceptible individuals, the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions. These changes can affect the gut-brain axis and the visceral sensitivity, disrupting the intestinal barrier, altering neuromuscular function, triggering persistent low inflammation, and sustaining the onset of IBS symptoms. There is no specific treatment strategy for PI-IBS. Different drug classes can be used to treat PI-IBS similar to patients with IBS in general, guided by their clinical symptoms. This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms. It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS. The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging. Several studies on PI-IBS animal models reported promising results. However, published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce. Future research is required.
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Affiliation(s)
- Vasile Valeriu Lupu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Cristina Mihaela Ghiciuc
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Gabriela Stefanescu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | | | - Alina Popp
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Maria Oana Sasaran
- Faculty of General Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures 540142, Romania
| | - Laura Bozomitu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Iuliana Magdalena Starcea
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Anca Adam Raileanu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Ancuta Lupu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
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Golla R, Vuyyuru S, Kante B, Kumar P, Thomas DM, Makharia G, Kedia S, Ahuja V. Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study. Clin Gastroenterol Hepatol 2023; 21:789-796.e1. [PMID: 36273799 PMCID: PMC9584755 DOI: 10.1016/j.cgh.2022.10.015] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/02/2022] [Accepted: 10/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.
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Affiliation(s)
- Rithvik Golla
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer Vuyyuru
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Peeyush Kumar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - David Mathew Thomas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
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Siyal M, Abbas Z, Ashraf J, Ali Qadeer M, Altaf A. Incidence and predisposing factors for de novo post-COVID-19 irritable bowel syndrome. Eur J Gastroenterol Hepatol 2023; 35:59-63. [PMID: 36468570 DOI: 10.1097/meg.0000000000002475] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Postinfectious irritable bowel syndrome (IBS) is a known entity. We evaluated the incidence of post-COVID-19 IBS in patients discharged from the hospital and analyzed its correlation with the clinical and laboratory parameters, and treatment during the hospital stay. METHODS Three hundred three COVID-19 hospitalized patients without prior history of IBS were prospectively followed after their discharge and were evaluated as per Rome-IV criteria for IBS. RESULTS One hundred seventy-eight patients were males (58.7%). The age range was 17-95 years (mean ± SD, 55.9 ± 15.8). A total of 194 (64%) had mild COVID-19, 74 (24.4%) had moderate COVID-19, whereas 35 (11.6%) had severe COVID-19 infection. Sixteen (5.3%) patients had concomitant GI symptoms during COVID-19 infection. IBS symptoms were found to be present in 32 (10.6%) patients, out of which 17 (53.13%) had diarrhea-predominant, 10 (31.25%) had constipation-predominant, and five (15.62%) had mixed-type IBS. Post-COVID-19 IBS was more common in the female sex (P < 0.001), concomitant GI symptoms with COVID-19 (P < 0.001), oxygen requirement (P = 0.015), deranged liver function tests at the time of admission (P = 0.002), high procalcitonin (P = 0.013), high C-reactive protein levels (P = 0.035); whereas negative correlation was found with remdesivir treatment (P = 0.047). After performing regression analysis, female sex (P < 0.001), oxygen requirement during hospital stay (P = 0.016), GI symptoms during COVID-19 infection (P < 0.001), and high procalcitonin levels (P = 0.017) were independently associated with post-COVID-19 IBS. CONCLUSION GI symptoms during active COVID-19 infection increase the chances of developing post-COVID-19 IBS. The risk of developing post-COVID-19 IBS increases in female patients, those requiring oxygen and having high procalcitonin levels during COVID-19 infection.
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Affiliation(s)
- Mehreen Siyal
- Department of Gastroenterology and Hepatology, Dr Ziauddin Hospital Clifton, Karachi, Pakistan
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Schneider KM, Kim J, Bahnsen K, Heuckeroth RO, Thaiss CA. Environmental perception and control of gastrointestinal immunity by the enteric nervous system. Trends Mol Med 2022; 28:989-1005. [PMID: 36208986 DOI: 10.1016/j.molmed.2022.09.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 05/25/2022] [Accepted: 09/07/2022] [Indexed: 12/12/2022]
Abstract
The enteric nervous system (ENS) forms a versatile sensory system along the gastrointestinal tract that interacts with most cell types in the bowel. Herein, we portray host-environment interactions at the intestinal mucosal surface through the lens of the enteric nervous system. We describe local cellular interactions as well as long-range circuits between the enteric, central, and peripheral nervous systems. Additionally, we discuss recently discovered mechanisms by which enteric neurons and glia respond to biotic and abiotic environmental changes and how they regulate intestinal immunity and inflammation. The enteric nervous system emerges as an integrative sensory system with manifold immunoregulatory functions under both homeostatic and pathophysiological conditions.
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Affiliation(s)
- Kai Markus Schneider
- Microbiology Department, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, PA, USA
| | - Jihee Kim
- Microbiology Department, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, PA, USA
| | - Klaas Bahnsen
- Microbiology Department, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, PA, USA
| | - Robert O Heuckeroth
- Department of Pediatrics, Children's Hospital of Philadelphia Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Christoph A Thaiss
- Microbiology Department, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, PA, USA.
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22
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Das BB, Panda AK, Patra MP, Nayak K. Study on the Role of Gastrointestinal Parasite in Irritable Bowel Syndrome Patients in a Tribal Region of India. Cureus 2022; 14:e26091. [PMID: 35875298 PMCID: PMC9295901 DOI: 10.7759/cureus.26091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2022] [Indexed: 11/05/2022] Open
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Hunskar GS, Rortveit G, Litleskare S, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study. Scand J Pain 2022; 22:348-355. [PMID: 34679267 DOI: 10.1515/sjpain-2021-0122] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting. METHODS A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ). RESULTS The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (p<0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37). CONCLUSIONS We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.
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Affiliation(s)
- Gunnhild S Hunskar
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Department of Dermatology, Haukeland University Hospital, Bergen, Norway
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Guri Rortveit
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Sverre Litleskare
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Geir Egil Eide
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Kurt Hanevik
- Norwegian National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Nina Langeland
- Norwegian National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Knut-Arne Wensaas
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
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Cooney J, Appiahene P, Findlay R, Al-Hillawi L, Rafique K, Laband W, Shandro B, Poullis A. COVID-19 infection causing residual gastrointestinal symptoms - a single UK centre case series. Clin Med (Lond) 2022; 22:181-183. [PMID: 38589187 DOI: 10.7861/clinmed.2021-0522] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Although COVID-19 was first recognised as an acute respiratory illness, extra-pulmonary manifestations are increasingly being recognised. Acute gastrointestinal side effects have been well reported with COVID-19 infection and are estimated to affect around 17% of patients. With COVID-19 still being a relatively new illness, the chronic gastrointestinal symptoms are less well characterised. Post-infectious irritable bowel syndrome (IBS) can occur following bacterial and viral infections, and with ACE-2 receptors being shown to be present in the gastrointestinal tract and SARS-Cov-2 RNA being present in stool, SARS-CoV-2 is now appreciated as an enteric pathogen. In our study, we survey acute and chronic gastrointestinal symptoms after COVID-19 infection. We have conducted one of the few UK studies on gastrointestinal symptoms, with the longest follow-up duration of 6 months. We have found that gastrointestinal symptoms are common at 6 months, affecting 43.8% of our patients. Further research is needed to explore whether this represents a new post-COVID-19 IBS, which has not previous been described in the literature, including its clinical course and response to any potential medical therapies.
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Affiliation(s)
- Joseph Cooney
- St George's University Hospitals NHS Foundation Trust, London, UK.
| | | | - Ross Findlay
- St George's University Hospitals NHS Foundation Trust, London, UK
| | - Lulia Al-Hillawi
- St George's University Hospitals NHS Foundation Trust, London, UK
| | - Khizar Rafique
- St George's University Hospitals NHS Foundation Trust, London, UK
| | - William Laband
- St George's University Hospitals NHS Foundation Trust, London, UK
| | - Benjamin Shandro
- St George's University Hospitals NHS Foundation Trust, London, UK
| | - Andrew Poullis
- St George's University Hospitals NHS Foundation Trust, London, UK
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Loosen SH, Kostev K, Jördens MS, Luedde T, Roderburg C. Overlap between irritable bowel syndrome and common gastrointestinal diagnoses: a retrospective cohort study of 29,553 outpatients in Germany. BMC Gastroenterol 2022; 22:48. [PMID: 35123405 PMCID: PMC8817597 DOI: 10.1186/s12876-022-02118-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/22/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Irritable bowel syndrome (IBS) represents the most common functional disorder of the gastrointestinal tract. Many patients with IBS display complex gastrointestinal (GI) symptoms leading to overlapping diagnosis of IBS and other GI diseases in many patients.
Methods
Using the Disease Analyzer database (IQVIA) featuring patients treated within 2010 and 2019 within 1240 general practices in Germany, we analyzed the prevalence of common GI diseases within 12 months prior to and after the first diagnosis of IBS.
Results
65,569 patients with an initial diagnosis of IBS were included into the analysis. Out of these, 29,553 patients had an observation time of at least 12 months prior to the first IBS diagnosis and at least 12 months after the first IBS diagnosis. Mean age was 48.8 (SD: 18.4) years, 65.0% were female. Notably, 16,164 (55%) of these patients had at least one preexisting diagnosis of another GI diseases within 12 months prior to the first IBS diagnosis. Most common overlapping diagnoses were intestinal infectious diseases (26%), gastritis/ duodenitis (21%), diseases of the esophagus (15%), non-infectious enteritis or colitis (7.4%), functional dyspepsia (6%) and ulcers (1.0%). Additionally, 12,048 (41%) received one of these diagnosis within 12 months after the first IBS diagnosis.
Conclusion
Our data provide evidence for a high overlap between IBS and other GI diagnoses. Moreover, we show that IBS is frequently diagnosed in patients with preexisting GI diseases, potentially putting into question the validity of IBS diagnosis at least in some cases.
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Joshee S, Lim L, Wybrecht A, Berriesford R, Riddle M. Meta-analysis and systematic review of the association between adverse childhood events and irritable bowel syndrome. J Investig Med 2022; 70:1342-1351. [PMID: 35086857 DOI: 10.1136/jim-2021-002109] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2022] [Indexed: 11/03/2022]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain, bowel habits alterations, constipation, and/or diarrhea. Adverse childhood experiences (ACEs) are events such as abuse and mental illness causing childhood trauma. Studies report higher prevalence of ACEs in patients with IBS with varied effect consistency and association strength. A systematic review and meta-analysis were conducted to evaluate current literature, assess heterogeneity and research gaps in this relationship. A search across PubMed, Embase, PsycINFO, and Google Scholar with keywords ('childhood adversity' OR 'childhood trauma' OR 'adverse childhood events') AND ('irritable colon' OR 'irritable bowel syndrome') yielded 106 studies. A restricted maximum likelihood model of 15 chosen studies with 272,686 participants found the association between ACEs and IBS to be uncertain given the considerable heterogeneity (I2=93.58%, p<0.001). Objective reporting methods for ACE and IBS, study size, and study quality explained some heterogeneity. Twelve studies showed publication bias (Egger's test, p<0.001), which further weakened interpretation. Gender-stratified subanalysis of three studies found ACEs associated with IBS in females (pOR=2.20, 95% CI (1.13 to 4.29), I2=66.90%) with substantial heterogeneity, but no association in males (pOR=1.30, 95% CI (0.62 to 2.78)). This meta-analysis explores the current literature to understand the biopsychosocial perspective of IBS and ACEs' role as risk factors. However, the risk of publication and design/study quality biases substantiates the need for further research. If an association is confirmed, further mechanistic research and development of targeted psychological therapies may be warranted.
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Affiliation(s)
- Shreeya Joshee
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | - Lauren Lim
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | - Alexis Wybrecht
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | | | - Mark Riddle
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
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Futagami S, Wakabayashi M. Pancreatic dysfunction and duodenal inflammatory responses coordinate with refractory epigastric pain including functional dyspepsia "A narrative review". J NIPPON MED SCH 2022; 89:255-262. [DOI: 10.1272/jnms.jnms.2022_89-311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Ankersen DV, Weimers P, Bennedsen M, Haaber AB, Fjordside EL, Beber ME, Lieven C, Saboori S, Vad N, Rannem T, Marker D, Paridaens K, Frahm S, Jensen L, Rosager Hansen M, Burisch J, Munkholm P. Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial. J Med Internet Res 2021; 23:e30291. [PMID: 34904950 PMCID: PMC8715363 DOI: 10.2196/30291] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/22/2021] [Accepted: 10/25/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. OBJECTIVE The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients' microbiota. METHODS Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). RESULTS A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was -126.50 (IQR -196.75 to -76.75) and for VSL#3 it was -130.00 (IQR -211.00 to -70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients' microbiota. CONCLUSIONS The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. TRIAL REGISTRATION ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622.
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Affiliation(s)
- Dorit Vedel Ankersen
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Petra Weimers
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Mette Bennedsen
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | | | - Eva Lund Fjordside
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | | | | | - Sanaz Saboori
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Nicolai Vad
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Terje Rannem
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Dorte Marker
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | | | - Suzanne Frahm
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Lisbeth Jensen
- Department of Dietetics, Herlev University Hospital, Herlev, Denmark
| | - Malte Rosager Hansen
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Pia Munkholm
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
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Abstract
Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.
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Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Maria-Ferreira D, Dallazen JL, Corso CR, Nascimento AM, Cipriani TR, da Silva Watanabe P, de Mello Gonçales Sant'Ana D, Baggio CH, de Paula Werner MF. Rhamnogalacturonan polysaccharide inhibits inflammation and oxidative stress and alleviates visceral pain. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104483] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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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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Coughlan S, Das A, O’Herlihy E, Shanahan F, O’Toole P, Jeffery I. The gut virome in Irritable Bowel Syndrome differs from that of controls. Gut Microbes 2021; 13:1-15. [PMID: 33602058 PMCID: PMC7899630 DOI: 10.1080/19490976.2021.1887719] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/28/2020] [Accepted: 01/25/2021] [Indexed: 02/08/2023] Open
Abstract
Irritable Bowel Syndrome (IBS), the most common gastrointestinal disorder, is diagnosed solely on symptoms. Potentially diagnostic alterations in the bacterial component of the gut microbiome (the bacteriome) are associated with IBS, but despite the known role of the virome (particularly bacteriophages), in shaping the gut bacteriome, few studies have investigated the virome in IBS. We performed metagenomic sequencing of fecal Virus-Like Particles (VLPs) from 55 patients with IBS and 51 control individuals. We detected significantly lower alpha diversity of viral clusters comprising both known and novel viruses (viral 'dark matter') in IBS and a significant difference in beta diversity compared to controls, but not between IBS symptom subtypes. The three most abundant bacteriophage clusters belonged to the Siphoviridae, Myoviridae, and Podoviridae families (Order Caudovirales). A core virome (defined as a cluster present in at least 50% of samples) of 5 and 12 viral clusters was identified in IBS and control subjects, respectively. We also identified a subset of viral clusters that showed differential abundance between IBS and controls. The virome did not co-vary significantly with the bacteriome, with IBS clinical subtype, or with Bile Acid Malabsorption status. However, differences in the virome could be related back to the bacteriome as analysis of CRISPR spacers indicated that the virome alterations were at least partially related to the alterations in the bacteriome. We found no evidence for a shift from lytic to lysogenic replication of core viral clusters, a phenomenon reported for the gut virome of patients with Inflammatory Bowel Disease. Collectively, our data show alterations in the virome of patients with IBS, regardless of clinical subtype, which may facilitate development of new microbiome-based therapeutics.
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Affiliation(s)
- S. Coughlan
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
| | - A. Das
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
- School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland
| | - E. O’Herlihy
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
| | - F. Shanahan
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
- APC Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland
| | - P.W. O’Toole
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
- School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland
- APC Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland
| | - I.B. Jeffery
- 4D Pharma Cork Limited, Cavanagh Pharmacy Building, University College Cork, National University of Ireland, Cork, Ireland
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Perisetti A, Goyal H, Gajendran M, Boregowda U, Mann R, Sharma N. Prevalence, Mechanisms, and Implications of Gastrointestinal Symptoms in COVID-19. Front Med (Lausanne) 2020; 7:588711. [PMID: 33195352 PMCID: PMC7662553 DOI: 10.3389/fmed.2020.588711] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/05/2020] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The infection started as an outbreak of pneumonia-like symptoms in Wuhan, China. Within a few weeks, it spread across the entire globe resulting in millions of cases and thousands of deaths. While respiratory symptoms and complications are well-defined and can be severe, non-respiratory symptoms of COVID-19 are increasingly being recognized. Gastrointestinal manifestations such as nausea, vomiting, diarrhea, and abdominal pain have been added to the list of common COVID-19 symptoms. Their prevalence has been increasing, probably due to increased recognition and experience with the pandemic. Furthermore, diarrhea and stool testing may change prevalence and transmission rates due to suspicion for fecal-oral transmission of the COVID-19. Due to this risk, various countries have started testing wastewater and sewage systems to examine its role in the spread of SARS-CoV-2 among communities. In this review article, we describe the common gastrointestinal manifestations in COVID-19, their prevalence based upon the current literature, and highlight the importance of early recognition and prompt attention. We also note the role of fecal-oral transmission. Furthermore, the mechanisms of these symptoms, the role of medications, and potential contributing factors are also elaborated.
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Affiliation(s)
- Abhilash Perisetti
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Hemant Goyal
- The Wright Center for Graduate Medical Education, Scranton, PA, United States
- Department of Internal Medicine, Mercer University School of Medicine, Macon, GA, United States
| | - Mahesh Gajendran
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States
| | - Umesha Boregowda
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, United States
| | - Rupinder Mann
- Saint Agnes Medical Center, Academic Hospitalists, Fresno, CA, United States
| | - Neil Sharma
- Division of Interventional Oncology and Surgical Endoscopy (IOSE), Parkview Cancer Institute, Fort Wayne, IN, United States
- Division of Interventional Oncology and Surgical Endoscopy, Indiana University School of Medicine, Fort Wayne, IN, United States
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Iacob T, Țățulescu DF, Lupșe MS, Dumitrașcu DL. Post-infectious irritable bowel syndrome after a laboratory-proven enteritis. Exp Ther Med 2020; 20:3517-3522. [PMID: 32905134 PMCID: PMC7464999 DOI: 10.3892/etm.2020.9018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 07/06/2020] [Indexed: 12/13/2022] Open
Abstract
There are scarce data on risk factors for post-infectious irritable bowel syndrome (PI-IBS). The objective of this study was to determine the risk factors of developing PI-IBS following an acute infectious gastroenteritis (AGE) episode in which, by laboratory tests, the etiological agent was isolated. The study was conducted on patients admitted to a tertiary center of infectious diseases during three consecutive years. The patients were divided into two groups: a group consisting of patients admitted with AGE (with an isolated etiological agent) and a control group consisting of patients admitted for an acute upper respiratory tract infection (URTI). The subjects were recalled in our center 6 months after the admission and were evaluated with Rome III IBS diagnostic questionnaire and Bristol Stool Form Scale. The questionnaires were paper printed and directly filled in by the subjects. The response rate in the case group was 5% and in the control group 100%. The prevalence of PI-IBS was higher in patients with AGE, presenting a relative risk (RR) of 4.16 [95% confidence interval (CI), 1.89-9.17], statistically significant (P<0.001) vs. URTI. From 28 female patients, 22 patients (79%) developed PI-IBS and from 17 male patients, 3 patients (18%) had developed PI-IBS with a risk of 4.4 (95% CI, 1.56-12.65), P<0.001. Regarding the infectious etiology of the AGE, Campylobacter jejuni had the highest risk of developing PI-IBS, RR=1.2 (95% CI, 0.13-3.11), P=0.04 compared with the other agents with a lower risk. The risk to develop PI-IBS after AGE infection is 4.16 higher than after URTI. Female sex is a risk factor for PI-IBS, 79% of the female patients developed PI-IBS after AGE. The incidence of PI-IBS is highest in patients with Campylobacter jejuni AGE compared with the other agents.
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Affiliation(s)
- Teodora Iacob
- Department of Infectious Diseases, ‘Iuliu Hațieganu’ University of Medicine and Pharmacy, 400348 Cluj-Napoca, Romania
| | - Doina F. Țățulescu
- Department of Infectious Diseases, ‘Iuliu Hațieganu’ University of Medicine and Pharmacy, 400348 Cluj-Napoca, Romania
| | - Mihaela S. Lupșe
- Department of Infectious Diseases, ‘Iuliu Hațieganu’ University of Medicine and Pharmacy, 400348 Cluj-Napoca, Romania
| | - Dan L. Dumitrașcu
- Second Medical Department, ‘Iuliu Hațieganu’ University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
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Balmus IM, Ciobica A, Cojocariu R, Luca AC, Gorgan L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. ACTA ACUST UNITED AC 2020; 56:medicina56040175. [PMID: 32295083 PMCID: PMC7230401 DOI: 10.3390/medicina56040175] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development.
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Affiliation(s)
- Ioana-Miruna Balmus
- Department of Interdisciplinary Research in Science, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, No. 11, 700506 Iași, Romania;
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Roxana Cojocariu
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
| | - Alina-Costina Luca
- Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 16th University Street, 700115 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Lucian Gorgan
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
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O' Donovan CM, Connor B, Madigan SM, Cotter PD, O' Sullivan O. Instances of altered gut microbiomes among Irish cricketers over periods of travel in the lead up to the 2016 World Cup: A sequencing analysis. Travel Med Infect Dis 2020; 35:101553. [PMID: 31935465 DOI: 10.1016/j.tmaid.2020.101553] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 12/18/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Changes and stresses experienced during travel have the potential to impact the gut microbiome, with travel implicated in the spread of antibiotic resistance genes across continents. The possibility of gut microbiome-mediated negative impacts arising from travel, and consequences for peak performance, would be of particular concern for elite athletes. METHODS Faecal samples were collected from male (N = 14) and female (N = 7) cricket players during the build-up to the 2016 Cricket World Cup. Baseline and post-travel samples were collected from all participants and subjected to 16S rRNA amplicon sequencing. Samples from a subset of participants (N = 4) were also analysed by shotgun metagenomic sequencing. RESULTS Analysis revealed a single travel time point as having the potential to have an impact on the gut microbiome. Reductions in alpha diversity following travel were observed, accompanied by shifts in the taxonomic profile of the gut microbiome. Antibiotic resistance and virulence genes were also identified as undergoing changes following travel. CONCLUSIONS This study reveals that periods of travel, in particular following gastrointestinal distress, may result in gut microbiome disruption. While this analysis was completed in athletes, the findings are applicable to all travelling individuals and considerations should be made surrounding travel in an attempt to reduce these changes.
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Affiliation(s)
- Ciara M O' Donovan
- Teagasc Food Research Centre, Moorepark, Fermoy, Co, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, Ireland
| | | | - Sharon M Madigan
- Sport Ireland Institute, National Sports Campus, Dublin 15, Ireland
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Co, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
| | - Orla O' Sullivan
- Teagasc Food Research Centre, Moorepark, Fermoy, Co, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
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37
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Wang Y, Zheng F, Liu S, Luo H. Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome. Gastroenterol Res Pract 2019; 2019:9759138. [PMID: 31885549 PMCID: PMC6914991 DOI: 10.1155/2019/9759138] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 09/10/2019] [Accepted: 11/07/2019] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.
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Affiliation(s)
- Yao Wang
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Fengling Zheng
- The Journal Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Shan Liu
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
| | - Huanhuan Luo
- School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, China
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38
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Herndon CC, Wang YP, Lu CL. Targeting the gut microbiota for the treatment of irritable bowel syndrome. Kaohsiung J Med Sci 2019; 36:160-170. [PMID: 31782606 DOI: 10.1002/kjm2.12154] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 10/20/2019] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.
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Affiliation(s)
- Charles C Herndon
- Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Yen-Po Wang
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Liang Lu
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Editorial: The Promise of Psychiatric Translational Research: Exploring How the Gut Can Influence Brain Development. J Am Acad Child Adolesc Psychiatry 2019; 58:1059-1061. [PMID: 31170444 DOI: 10.1016/j.jaac.2019.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/28/2019] [Indexed: 11/23/2022]
Abstract
How the gastrointestinal (GI) tract can influence the development and functioning of the central nervous system is one of the hottest translational research topics today. In animal studies, GI infections have been linked to enteric inflammation, disrupted intestinal permeability, and changes in diversity in the gut microbiome as well as brain dysfunction.1 In humans, infectious gastroenteritis has been associated with modified composition of the gut microbiome and systemic inflammation.2 Although gastroenteritis has not been causally linked to dysregulation of the brain in humans, it has been associated with later chronic GI conditions such as irritable bowel syndrome, which is often accompanied by anxiety and depression.2-4 In other human studies, microbiome dysbiosis has been associated with significantly increased the risk for later systemic inflammation and brain dysfunction manifested as changes in emotions, behaviors, pain perception, and cognitions.5,6 Most studies investigating these relationships have focused on adult cohorts and are often cross-sectional in design nature. The study by Parent et al.7 is the first longitudinal study to evaluate whether repeated episodes of gastroenteritis during early childhood predicts behavioral problems in later childhood and mental illness during adolescence. In addition, it has an exploratory mechanistic objective: whether systemic inflammation in later childhood and adolescence moderates this brain-gut relationship.
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40
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van Thiel IAM, Botschuijver S, de Jonge WJ, Seppen J. Painful interactions: Microbial compounds and visceral pain. Biochim Biophys Acta Mol Basis Dis 2019; 1866:165534. [PMID: 31634534 DOI: 10.1016/j.bbadis.2019.165534] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 08/12/2019] [Accepted: 08/13/2019] [Indexed: 12/18/2022]
Abstract
Visceral pain, characterized by abdominal discomfort, originates from organs in the abdominal cavity and is a characteristic symptom in patients suffering from irritable bowel syndrome, vulvodynia or interstitial cystitis. Most organs in which visceral pain originates are in contact with the external milieu and continuously exposed to microbes. In order to maintain homeostasis and prevent infections, the immune- and nervous system in these organs cooperate to sense and eliminate (harmful) microbes. Recognition of microbial components or products by receptors expressed on cells from the immune and nervous system can activate immune responses but may also cause pain. We review the microbial compounds and their receptors that could be involved in visceral pain development.
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Affiliation(s)
- I A M van Thiel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - S Botschuijver
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - W J de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands
| | - J Seppen
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, Meibergdreef 69, 1105 BK Amsterdam, the Netherlands.
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Sadeghi A, Biglari M, Nasseri Moghaddam S. Post-infectious Irritable Bowel Syndrome: A Narrative Review. Middle East J Dig Dis 2019; 11:69-75. [PMID: 31380002 PMCID: PMC6663289 DOI: 10.15171/mejdd.2019.130] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
The Irritable bowel syndrome (IBS) is a functional disorder of alimentary system, which may be caused by infectious gastroenteritis determined as post infectious irritable bowel syndrome (PI-IBS). The prevalence of PI-IBS is reported to be 4-36% in patients with infectious gastroenteritis. The exact mechanism leading to PI-IBS is not fully understood and some factors pertaining to infectious agent and host response may have a role. Rome IV diagnostic criteria provided new definition for PI-IBS. Though it is now considered a well-defined functional disorder of gastrointestinal system, no specific treatment is yet available for PI-IBS. This article reviews the latest issues on these heading about PI-IBS.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Biglari
- Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Siavosh Nasseri Moghaddam
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Abstract
Lactobacillus rhamnosus GG (LGG) was the first strain belonging to the genus Lactobacillus to be patented in 1989 thanks to its ability to survive and to proliferate at gastric acid pH and in medium containing bile, and to adhere to enterocytes. Furthermore LGG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity. Moreover LGG thanks to its lectin-like protein 1 and 2 inhibits some pathogens such as Salmonella species. Finally LGG is able to promote type 1 immune-responsiveness by reducing the expression of several activation and inflammation markers on monocytes and by increasing the production of interleukin-10, interleukin-12 and tumor necrosis factor-α in macrophages. A large number of research data on Lactobacillus GG is the basis for the use of this probiotic for human health. In this review we have considered predominantly randomized controlled trials, meta-analysis, Cochrane Review, guide lines of Scientific Societies and anyway studies whose results were evaluated by means of relative risk, odds ratio, weighted mean difference 95% confidence interval. The effectiveness of LGG in gastrointestinal infections and diarrhea, antibiotic and Clostridium difficile associated diarrhea, irritable bowel syndrome, inflammatory bowel disease, respiratory tract infections, allergy, cardiovascular diseases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cystic fibrosis, cancer, elderly end sport were analyzed.
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43
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Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: What does the future hold? World J Gastroenterol 2019; 25:552-566. [PMID: 30774271 PMCID: PMC6371005 DOI: 10.3748/wjg.v25.i5.552] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Revised: 12/19/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023] Open
Abstract
Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.
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Affiliation(s)
- Kashif Mukhtar
- Centre of Excellence in Women and Child Health, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Hasham Nawaz
- Department of Medicine, Section of Gastroenterology, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Shahab Abid
- Department of Medicine, Section of Gastroenterology, Aga Khan University, Karachi, Sindh 74800, Pakistan
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44
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Zhu X, Liu Z, Qin Y, Niu W, Wang Q, Li L, Zhou J. Analgesic Effects of Electroacupuncture at St25 and Cv12 in a Rat Model of Postinflammatory Irritable Bowel Syndrome Visceral Pain. Acupunct Med 2018; 36:240-246. [DOI: 10.1136/acupmed-2016-011320] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2017] [Indexed: 12/20/2022]
Abstract
Background Treatment with electroacupuncture (EA) at ST25 and CV12 has a significant analgesic effect on postinflammatory irritable bowel syndrome (PI-IBS) visceral pain. Enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine (5-HT)) are important in the development of visceral hyperalgesia. Objective To investigate the analgesic effect and underlying mechanisms of EA at ST25 and CV12 on the treatment of trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS visceral hyperalgesia in rats. Methods After EA at ST25 and CV12, changes in abdominal withdrawal reflex (AWR), electromyography (EMG) recordings, colonic EC cell numbers, and expression of tryptophan hydroxylase (TPH), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) of TNBS-induced PI-IBS visceral hyperalgesia in rats were examined. Results The results of AWR tests and EMG recordings indicated a significant analgesic effect of EA stimulation at ST25 and CV12on PI-IBS visceral hyperalgesia (p<0.05). In addition, the increased EC cell numbers and colonic expression of TPH and 5-HT in rats with TNBS-induced PI-IBS visceral hyperalgesia were significantly reduced by EA (p<0.05). Conclusions EA stimulation at ST25 and CV12 can attenuate visceral hyperalgesia. This analgesic effect may be mediated via reduction of both colonic EC cell number and 5-HT concentration.
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Affiliation(s)
- Xianwei Zhu
- Innovation Research Centre of Acupuncture combined with Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Zhibin Liu
- Innovation Research Centre of Acupuncture combined with Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
- Department of Acupuncture and Moxibustion, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Yifei Qin
- Innovation Research Centre of Acupuncture combined with Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Wenmin Niu
- Innovation Research Centre of Acupuncture combined with Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
- Department of Acupuncture and Moxibustion, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Qiang Wang
- Innovation Research Centre of Acupuncture combined with Medicine, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Lu Li
- Department of Acupuncture and Moxibustion, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
| | - Jing Zhou
- College of Public Hygiene, Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Economic Zone, Shaanxi Province, China
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Schultz BM, Salazar GA, Paduro CA, Pardo-Roa C, Pizarro DP, Salazar-Echegarai FJ, Torres J, Riedel CA, Kalergis AM, Álvarez-Lobos MM, Bueno SM. Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation. Front Immunol 2018; 9:1166. [PMID: 29896196 PMCID: PMC5986922 DOI: 10.3389/fimmu.2018.01166] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 05/09/2018] [Indexed: 12/12/2022] Open
Abstract
Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium) infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS) and interleukin (IL)-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2). Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.
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Affiliation(s)
- Bárbara M Schultz
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Geraldyne A Salazar
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Carolina A Paduro
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Catalina Pardo-Roa
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniela P Pizarro
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco J Salazar-Echegarai
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Javiera Torres
- Departamento de Anatomía Patológica, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Claudia A Riedel
- Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile
| | - Alexis M Kalergis
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.,Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Manuel M Álvarez-Lobos
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Susan M Bueno
- Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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46
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Blastocystis subtypes and their association with Irritable Bowel Syndrome. Med Hypotheses 2018; 116:4-9. [PMID: 29857906 DOI: 10.1016/j.mehy.2018.04.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 04/10/2018] [Accepted: 04/10/2018] [Indexed: 12/13/2022]
Abstract
Blastocystis spp. is a common intestinal protozoan that affects humans and animals. The role of this parasite as a pathogen is still controversial and it is suspected to be linked to Irritable Bowel Syndrome (IBS), a functional bowel disorder characterized by chronic or recurrent abdominal pain associated with altered intestinal habits. A broad search in electronic databases, libraries, portals of journals, etc. for reports on the association between the parasite and IBS without language restriction was performed. The selection was not restricted by date, but articles published in the last seven years were given preference. We investigated the evidence regarding Blastocystis and IBS coexistence as well as the implications of the parasite in pathogenesis and clinical manifestations. Only standardized parasitological tools, supplemented by epidemiological analysis, will be able to clarify whether parasite carriage could be connected to IBS and its status as a human pathogen. Although a variation in pathogenicity and virulence between subtypes has been confirmed, Blastocystis can only be considered an indicator of dysbiosis. Accurate diagnoses of this parasitic eukaryote, specifically at genotypic and phenotypic levels, as well as the complete analysis of the intestinal microbial communities, have to be included in the protocol of those patients with IBS.
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Kilian E, Suchodolski JS, Hartmann K, Mueller RS, Wess G, Unterer S. Long-term effects of canine parvovirus infection in dogs. PLoS One 2018; 13:e0192198. [PMID: 29547647 PMCID: PMC5856261 DOI: 10.1371/journal.pone.0192198] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 01/19/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Canine parvovirus (CPV) is the most important viral cause of acute canine enteritis leading to severe damage of the intestinal barrier. It has been speculated that dogs might develop chronic disorders after surviving CPV infection. However, no studies regarding the long-term implications of CPV infection have been published to date. The aim of this study was to evaluate whether dogs that have survived CPV infection will have an increased risk for developing chronic gastroenteritis, atopic dermatitis, or cardiac disease. METHODOLOGY/PRINCIPAL FINDINGS Dogs that had been treated at the Clinic of Small Animal Medicine, LMU Munich, for CPV infection for which a follow-up of at least 12 months was available, were included in the study. Owners completed a questionnaire on the presence of chronic gastrointestinal and cutaneous signs, cardiac disease, and other potential disorders. An identical questionnaire was sent to owners of matched control dogs during the same time period. Seventy-one questionnaires of dogs with CPV infection and 67 of control dogs were analyzed. Significantly more CPV-infected dogs (30/71) compared to control dogs (8/67) had developed chronic gastrointestinal signs later in their lives (P < 0.001). No significant differences were observed regarding skin diseases (P = 1), cardiac problems (P = 0.160), or any other diseases (P = 0.173) later in life. CONCLUSIONS Results of this study suggest that dogs that survive CPV infection have a significantly higher risk (odds ratio = 5.33) for developing a chronic gastrointestinal disease. Further prospective studies to identify the trigger for the development of chronic diarrhoea and possible targeted treatment strategies are needed.
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Affiliation(s)
- Elena Kilian
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
- * E-mail:
| | - Jan S. Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, Texas, United States of America
| | - Katrin Hartmann
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Ralf S. Mueller
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Gerhard Wess
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Stefan Unterer
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
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48
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Harper A, Naghibi MM, Garcha D. The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome. Foods 2018; 7:E13. [PMID: 29373532 PMCID: PMC5848117 DOI: 10.3390/foods7020013] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/18/2018] [Accepted: 01/24/2018] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome is a highly prevalent gastrointestinal disorder that threatens the quality of life of millions and poses a substantial financial burden on healthcare systems around the world. Intense research into the human microbiome has led to fascinating discoveries which directly and indirectly implicate the diversity and function of this occult organ in irritable bowel syndrome (IBS) pathophysiology. The benefit of manipulating the gastrointestinal microbiota with diet and probiotics to improve symptoms has been demonstrated in a wealth of both animal and human studies. The positive and negative mechanistic roles bacteria play in IBS will be explored and practical probiotic and dietary choices offered.
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Affiliation(s)
- Ashton Harper
- Protexin, Medical Affairs, Probiotics International Ltd., Lopen Head, Somerset TA13 5JH, UK.
| | - Malwina M Naghibi
- Protexin, Medical Affairs, Probiotics International Ltd., Lopen Head, Somerset TA13 5JH, UK.
| | - Davinder Garcha
- Protexin, Medical Affairs, Probiotics International Ltd., Lopen Head, Somerset TA13 5JH, UK.
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49
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Stephen DM, Barnett AG. Using Microsimulation to Estimate the Future Health and Economic Costs of Salmonellosis under Climate Change in Central Queensland, Australia. ENVIRONMENTAL HEALTH PERSPECTIVES 2017; 125:127001. [PMID: 29233795 PMCID: PMC5963579 DOI: 10.1289/ehp1370] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 11/08/2017] [Accepted: 11/08/2017] [Indexed: 05/31/2023]
Abstract
BACKGROUND The incidence of salmonellosis, a costly foodborne disease, is rising in Australia. Salmonellosis increases during high temperatures and rainfall, and future incidence is likely to rise under climate change. Allocating funding to preventative strategies would be best informed by accurate estimates of salmonellosis costs under climate change and by knowing which population subgroups will be most affected. OBJECTIVE We used microsimulation models to estimate the health and economic costs of salmonellosis in Central Queensland under climate change between 2016 and 2036 to inform preventative strategies. METHODS We projected the entire population of Central Queensland to 2036 by simulating births, deaths, and migration, and salmonellosis and two resultant conditions, reactive arthritis and postinfectious irritable bowel syndrome. We estimated salmonellosis risks and costs under baseline conditions and under projected climate conditions for Queensland under the A1FI emissions scenario using composite projections from 6 global climate models (warm with reduced rainfall). We estimated the resulting costs based on direct medical expenditures combined with the value of lost quality-adjusted life years (QALYs) based on willingness-to-pay. RESULTS Estimated costs of salmonellosis between 2016 and 2036 increased from 456.0 QALYs (95% CI: 440.3, 473.1) and AUD29,900,000 million (95% CI: AUD28,900,000, AUD31,600,000), assuming no climate change, to 485.9 QALYs (95% CI: 469.6, 503.5) and AUD31,900,000 (95% CI: AUD30,800,000, AUD33,000,000) under the climate change scenario. CONCLUSION We applied a microsimulation approach to estimate the costs of salmonellosis and its sequelae in Queensland during 2016-2036 under baseline conditions and according to climate change projections. This novel application of microsimulation models demonstrates the models' potential utility to researchers for examining complex interactions between weather and disease to estimate future costs. https://doi.org/10.1289/EHP1370.
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Affiliation(s)
- Dimity Maree Stephen
- Institute of Health and Biomedical Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Adrian Gerard Barnett
- Institute of Health and Biomedical Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Queensland, Australia
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Chen Q, Ren Y, Lu J, Bartlett M, Chen L, Zhang Y, Guo X, Liu C. A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response. Nutrients 2017; 9:nu9121341. [PMID: 29232851 PMCID: PMC5748791 DOI: 10.3390/nu9121341] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 11/24/2017] [Accepted: 12/07/2017] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder yet it still lacks effective prevention therapies. The aim of this study is to determine whether a novel prebiotic blend (PB) composed of fructo-oligosaccharide (FOS), galactooligosaccharide (GOS), inulin and anthocyanins could be effective in preventing the development of IBS. We explored the possible mechanisms both in animal and in cells. Post-infectious IBS models in C57BL/6 mice were established and were pretreated with the PB, PB and probiotic strains 8 weeks in advance of infection. Eight weeks after infection, intestinal tissues were collected for assessing histomorphology, visceral sensitivity, barrier function, pro-inflammatory cytokines expression and proteomics analysis. Fecal samples were also collected for microbiota analysis. The pro-inflammatory cytokines expression in Caco-2 cells were evaluated after co-incubation with PB and Salmonella typhimurium 14028. The results showed that PB significantly decreased the pro-inflammatory cytokines both in infected Caco-2 cells and PI-IBS models. The loss of body weight, decreased expression of tight junction protein Occludin (OCLN), and changes of the microbiota composition induced by infections could be greatly improved by PB intervention (p < 0.05). The proteomics analysis revealed that this function was associated with Peroxisome proliferator-activated receptor (PPAR)γ pathway.
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Affiliation(s)
- Qian Chen
- Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Yiping Ren
- Center for Anti-Aging Research, Nu Skin Enterprises, Shanghai 201401, China.
| | - Jihong Lu
- Center for Anti-Aging Research, Nu Skin Enterprises, Shanghai 201401, China.
| | - Mark Bartlett
- Nu Skin Enterprises Anti-Aging Research Center, Provo, UT 84601, USA.
| | - Lei Chen
- Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Yan Zhang
- Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Xiaokui Guo
- Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Chang Liu
- Department of Microbiology and Immunology, Institutes of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
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