Risk factors for developing irritable bowel syndrome: systematic umbrella review of reviews.

We searched MEDLINE, Embase, and Cochrane library databases from database inception to November 11, 2024. This current systematic review was performed with reference to the latest Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [ 22 ], with search terms including but were not limited to “Irritable Bowel Syndrome”, “Risk Factors” and “Systematic Review”. The search strategy was developed in consultation with an information management specialist, and the full search strategy is available in the Supplementary Material (Table S1). The study protocol was prospectively registered in PROSPERO (registration number CRD42023493739). All search results were imported into Covidence (Melbourne, Victoria, Australia) for the identification and removal of duplicates. To ensure consistency and rigour, the Covidence software was set to ensure that each article was reviewed independently by two reviewers independently at every stage, including both the title and abstract screening and the full-text review phases. For the title and abstract screening, five reviewers (FS, TOSK, ASPT, JQ, and DTL) were involved to ensure comprehensive coverage of the large number of search results and to identify a wider pool of potentially eligible studies before reaching consensus with a senior reviewer. Discrepancies at both stages were resolved through consensus with a senior author (QXN or KTHS). Only original systematic reviews of observational studies, including cohort, case–control and cross-sectional studies, or interventional studies in English or with an English translation were included. Non-systematic narrative reviews, editorials, opinion pieces and case reports were excluded from the study. Studies which investigated primary risk factors of IBS in previously healthy individuals which may include but were not limited to dietary factors, psychosocial factors, gastrointestinal infections, certain medication uses, lifestyle factors such as physical activity and sleep patterns, genetic predisposition, environmental factors and socioeconomic factors. Studies without a clear diagnosis of IBS, those that examined non-specific exposures, interventions for managing IBS, secondary risk factors (that might affect the course or management of IBS), animal studies, or those involving pediatric populations were excluded. The primary outcomes of interest in this paper include the measure of the strength of association between the defined risk factor(s) and the development of IBS, reported in relative risks (RR), odds ratios (OR), or prevalence/incidence rates in the reviewed studies. Narrative synthesis of collected data was conducted. Study characteristics, populations, risk factors examined, IBS outcome measures and key findings would be extracted from included papers, with similar risk factors being grouped together (e.g. dietary, psychological, early life exposures) across different studies. We also provided a summary of the evidence supporting each category and evaluated the strength of association with developing IBS. The Measurement Tool to Assess Systematic Reviews (AMSTAR2) tool was used for quality assessment and check for robustness of evidence provided in the studies included in this systematic review [ 23 ]. The AMSTAR2 tool comprises 16 items that evaluate various aspects of a systematic review’s methodology, such as the comprehensiveness of the literature search, the justification of excluded studies, the appropriateness of the methods used to synthesize results, and the assessment of the risk of bias in individual studies. This produces an overall grading of an article: high, moderate, low or critically low. To comprehensively evaluate the level of evidence for frequently mentioned risk factors, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used [ 24 ]. The GRADE framework evaluates evidence in five domains, namely: Risk of bias, inconsistency, indirectness, imprecision and publication bias.

The initial search from the Embase, MEDLINE and Cochrane Library databases yielded 4903 articles. References were imported into Covidence, resulting in the automated removal of 1119 duplicates. Further screening resulted in the manual removal of 3784 articles not meeting the including criteria during the title and abstract sieve, with 101 articles remaining for full-text screening. Grey literature was also searched, identifying two articles for review, one of which was not retrievable. Finally, a total of 69 systematic reviews [ 2 , 25 – 92 ] published between 2002 and 2024 were included. The process of literature search and article selection is summarized in Fig. 1 . A summarized list of studies and their reason(s) for exclusion after full-text review is detailed in the Supplementary Material (Table S2). Fig. 1 PRISMA flowchart showing the study search and selection process PRISMA flowchart showing the study search and selection process As rated using the AMSTAR2 tool, all studies were categorized as “low” (15 studies, 22%) or “critically low” (53 studies, 77%) or moderate (1 study, 1%). More than half the studies adhered to the population, intervention, comparator group, outcome (PICO) framework for research questions, explained the selection of study designs for inclusion, performed study selection and data extraction in duplicate, report sources of funding, utilize the appropriate statistical combination of results in meta-analysis, provide satisfactory explanation and discussion of heterogeneity, adequately investigate publication bias and report potential conflict of interest, including funding for the study. More than half, at least partially, adhered to having an explicit statement of review methods and reporting deviation from study protocol, have a comprehensive literature search strategy, describe included studies in adequate detail and use a satisfactory technique for assessing risk of bias (ROB) in individual studies. However, the most common critical flaws were not prospectively registering their study protocols, providing a list of excluded studies and justifying the exclusions and providing an account for the ROB in individual studies when interpreting/discussing the results of the review. The details of the AMSTAR2 results of included reviews are explained in Table  1 . Table 1 AMSTAR2 quality assessment for reviews included Author, Year Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 Q16 Overall Quality Abedi et al. 2021 [ 25 ] Yes No No Yes Yes Yes No Partial yes No Yes Yes No No Yes Yes Yes Critically low Afari et al. 2014 [ 90 ]  Yes No No Yes Yes Yes No No No No Yes No Yes Yes Yes Yes Critically low Areeshi et al. 2013 [ 26 ]  Yes Yes Yes Partial yes No Yes No Yes No Yes No No No Yes Yes Yes Critically low Almansour et al. 2024 [ 87 ] Yes No No Partial yes Yes No No Partial yes No Yes - - No No - Yes Critically low Bernard et al. 2023 [ 86 ] Yes No No Partial yes Yes No No No Partial yes Yes Yes Yes Yes Yes Yes Yes Critically low Chen et al. 2020 [ 28 ]  Yes Partial yes No Partial yes Yes Yes No Yes Yes Yes - - Yes Yes - Yes Low Chitkara et al. 2013 [ 29 ] Yes No No No No No No Partial yes No Yes - - No Yes - Yes Critically low Creed et al. 2019 [ 30 ] Yes No Yes Partial yes No No No Partial yes Yes No - - No No - No Critically low Czogalla et al 2015 [ 31 ] Yes Partial yes Yes No Yes Yes No Yes Partial yes Yes Yes Yes Yes No No Yes Critically low El-Serag et al. 2009 [ 32 ]  Yes No No Partial yes Yes No No Partial yes No Yes - - No No - Yes Critically low Fan et al. 2022 [ 33 ] Yes Partial yes Yes Partial yes Yes Yes No No No Yes Yes No No Yes Yes Yes Critically low Ford et al. 2009 [ 34 ] Yes No No Partial yes Yes Yes No Partial yes No Yes No No No No Yes Yes Critically low Gandhi et al 2021 [ 35 ] Yes Partial yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Low Guo et al 2021 [ 36 ] Yes Yes Yes Partial yes Yes Yes No Yes Partial yes Yes Yes Yes Yes Yes Yes Yes Low Halvorson et al. 2006 [ 37 ] Yes No No Partial yes Yes Yes No Yes No No No No No Yes Yes Yes Critically low Hawkings et al 2023 [ 39 ] Yes Yes Yes Partial yes Yes Yes No Yes Partial yes Yes - - Yes Yes - Yes Low Hanel et al. 2021 [ 38 ] Yes Partial yes Yes Yes Yes Yes No Yes Yes Yes - - Yes No - Yes Low Ibrahim 2016 [ 40 ] Yes Partial yes Yes Partial yes No No No No No No - - No No - Yes Critically low Jiang et al. 2017 [ 41 ] Yes No No Partial yes No Yes No Partial yes Yes No Yes No No Yes Yes Yes Critically low Joshee et al. 2022 [ 42 ] Yes No Yes Yes Yes No No Partial yes Partial yes Yes Yes Yes Yes Yes Yes Yes Critically low Junaid et al. 2023 [ 85 ] Yes No No Partial yes Yes Yes No Partial yes Yes Yes Yes No Yes Yes No Yes Critically low Keithlin et al 2014 [ 43 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Partial yes No Yes Yes Yes Yes No Yes Critically low Kerkhoven et al. 2007 [ 72 ] Yes No Yes Partial yes No No No Partial yes No No No No No No Yes Yes Critically low Kim et al. 2020 [ 44 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Partial yes Yes Yes No No Yes Yes Yes Critically low Klem et al. 2017 [ 45 ] Yes No Yes Yes Yes Yes No Yes no Yes Yes No No Yes Yes Yes Critically low Leech et al. 2018 [ 91 ] Yes No No Yes Yes Yes No Yes Partial yes No - - Yes Yes - Yes Critically low Li et al. 2020 [ 46 ] Yes No No Partial yes Yes Yes No Partial yes No Yes Yes Yes No Yes No Yes Critically low Liu et al. 2022 [ 47 ] Yes Yes no Partial yes No Yes No Partial yes Yes No Yes Yes Yes Yes Yes Yes Low Lovell et al. 2012a [ 49 ] Yes No Yes Yes No Yes No Partial yes No No No No No No Yes Yes Critically low Lovell et al. 2012b [ 48 ] Yes Partial yes Yes Partial yes Yes Yes No Yes No No Yes No No Yes Yes Yes Critically low Low et al. 2020 [ 50 ] Yes No Yes Partial yes Yes No No Partial yes - No - - Yes No - Yes Critically low Manzoli et al. 2017 [ 51 ] Yes No Yes Partial yes Yes No No Partial yes No No No No No No No Yes Critically low Marasaco et al. 2023 [ 52 ] Yes Partial yes No Partial yes Yes Yes No Partial yes Partial yes Yes Yes Yes Yes Yes Yes Yes Low Mathur et al. 2024 [ 53 ] Yes Yes Yes Partial yes Yes Yes No Yes Yes No Yes Yes No No No Yes Critically low Motawea et al. 2023 [ 54 ] Yes Partial yes Yes Partial yes Yes Yes No Partial yes Partial yes No Yes No No Yes No Yes Critically low Nastaskin et al. 2006 [ 55 ] Yes Partial yes Yes Yes Yes Yes No No Yes No - - Yes Yes - Yes Critically low Ng et al. 2018 [ 57 ] Yes Partial yes Yes Yes Yes Yes No Yes Partial yes Yes Yes No No Yes Yes Yes Critically low Ng et al. 2019 [ 56 ] Yes Yes Yes Yes Yes No No Partial yes No No No No Yes Yes Yes Yes Critically low Ng et al. 2024 [ 89 ] Yes Yes Yes Yes Yes Yes Partial Yes Yes Yes Yes Yes Yes Yes No - Yes Moderate Nikolova et al. 2022 [ 58 ] Yes Partial yes Yes Partial yes Yes Yes No Yes No No Yes No No Yes No Yes Critically low Pan et al. 2014 [ 59 ] Yes No Yes Partial yes Yes Yes No Partial yes No No Yes No No Yes Yes No Critically low Park et al. 2005 [ 60 ] Yes No No No No No No No Partial yes Yes - - No No - No Critically low Pickett-Blakely et al. 2014 [ 61 ] Yes No Yes Partial yes No No No Partial yes Yes No - - No Yes - No Critically low Qin et al. 2013 [ 62 ] Yes Partial yes Yes Partial yes Yes Yes No No Yes No Yes No No Yes Yes No Critically low Rostami et al. 2017 [ 63 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Low Saha et al. 2022 [ 64 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Yes Yes Yes Yes Yes No No No Critically low Saidi et al. 2020 [ 65 ] Yes Yes Yes Yes Yes Yes No Partial yes Yes Yes Yes Yes No Yes No Yes Critically low Schwille-Kiuntke et al. 2015 [ 66 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Partial yes Yes Yes No No Yes Yes Yes Critically low Sibelli et al. 2016 [ 67 ] Yes Yes Yes Partial yes Yes Yes No Yes Partial yes Yes Yes Yes No Yes Yes Yes Critically low Sirri et al. 2017 [ 68 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Partial yes Yes - - No Yes - Yes Critically low Silva et al. 2023 [ 84 ] Yes No No No No No No Partial yes No No - - No No - Yes Critically low Stanculete et al. 2021 [ 69 ] Yes Partial yes Yes Partial yes Yes Yes No Yes No Yes - - No No - Yes Critically low Svendsen et al. 2019 [ 70 ] Yes Yes Yes Yes No No No Yes Yes No Yes No No No Yes No Critically low Tak et al. 2011 [ 92 ] Yes No No Yes Yes Yes No No No No Yes No Yes Yes Yes Yes Critically low Thabane et al. 2007 [ 71 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Yes No Yes No Yes Yes Yes Yes Low Valencia et al. 2022 [ 2 ] Yes Partial yes Yes Partial yes No Yes No No Yes Yes - - No No - Yes Critically low Wang et al. 2019 [ 73 ] Yes Partial yes No Partial yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Low Wang et al. 2022a [ 74 ] Yes Partial yes Yes Partial yes Yes Yes No Partial yes Yes Yes Yes Yes Yes Yes No Yes Critically low Wang et al. 2022b [ 75 ] Yes Yes Yes Partial yes Yes Yes No Partial yes Yes Yes Yes No No Yes Yes Yes Critically low Wang et al. 2023 [ 76 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Yes Yes Yes No No Yes Yes Yes Critically low Wang et al. 2023 [ 88 ] Yes Yes No Yes No No No Yes Partial yes Yes Yes Yes Yes Yes Yes Yes Low Whitehead et al. 2002 [ 77 ] Yes Partial yes Yes No Yes No No No No No - - No No - Yes Critically low Wongtrakul et al. 2022 [ 78 ] Yes Partial yes Yes Partial yes Yes Yes No Yes Partial yes Yes Yes Yes Yes Yes Yes Yes Low Yang et al. 2022a [ 79 ] Yes Partial yes Yes Partial yes Yes Yes No Partial yes Yes No Yes No No Yes Yes Yes Critically low Yang et al. 2022b [ 27 ] Yes partial yes Yes Partial yes Yes Yes No Yes Yes No Yes No yes No Yes Yes Low Zhang et al. 2014 [ 80 ] Yes Partial yes Yes Partial yes Yes Yes No Partial yes Partial yes No Yes Yes Yes Yes Yes Yes Low Zhu et al. 2014 [ 81 ] Yes No Yes Partial yes Yes No No Partial yes No No No No No No No Yes Critically low Zhu et al. 2019 [ 82 ] Yes Partial yes Yes Partial yes Yes Yes No Partial yes Partial yes Yes Yes Yes Yes Yes Yes Yes Low Zhuang et al. 2017 [ 83 ] Yes Partial yes Yes Partial yes Yes Yes No Yes No No Yes Yes Yes Yes No No Critically low Legend: Q1: Did the research questions and inclusion criteria for the review include the components of PICO (population, intervention, comparator group and outcome)? Q2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol? Q3: Did the review authors explain their selection of the study designs for inclusion in the review? Q4: Did the review authors use a comprehensive literature search strategy? Q5: Did the review authors perform study selection in duplicate? Q6: Did the review authors perform data extraction in duplicate? Q7: Did the review authors provide a list of excluded studies and justify the exclusions? Q8: Did the review authors describe the included studies in adequate detail? Q9: Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? Q10: Did the review authors report on the sources of funding for the studies included in the review? Q11: If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results? Q12: If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis Q13: Did the review authors account for RoB in individual studies when interpreting/ discussing the results of the review? Q14: Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? Q15: If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review? Q16: Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review? AMSTAR2 quality assessment for reviews included Legend: Q1: Did the research questions and inclusion criteria for the review include the components of PICO (population, intervention, comparator group and outcome)? Q2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol? Q3: Did the review authors explain their selection of the study designs for inclusion in the review? Q4: Did the review authors use a comprehensive literature search strategy? Q5: Did the review authors perform study selection in duplicate? Q6: Did the review authors perform data extraction in duplicate? Q7: Did the review authors provide a list of excluded studies and justify the exclusions? Q8: Did the review authors describe the included studies in adequate detail? Q9: Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? Q10: Did the review authors report on the sources of funding for the studies included in the review? Q11: If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results? Q12: If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis Q13: Did the review authors account for RoB in individual studies when interpreting/ discussing the results of the review? Q14: Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? Q15: If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review? Q16: Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review? The included reviews have analysed the literature across some 30 databases, with most studies analysing literature from PubMed, MEDLINE, Embase, Cochrane, Web of Science, Scopus and Google Scholar. Collectively, the literature was searched from inception to 2023. Most of the reviews analysed purely observational studies, while three reviews [ 27 , 54 , 55 ] included interventional studies in their analysis. The risk factors identified from the included reviews have been grouped into eight common themes listed below. The summary of findings is shown in Table  2 . Table 2 Summary of included reviews and their findings Author, year Factor(s) studied Search database(s) Search dates Type(s) of studies included Number of studies of included Significant risk factors a Overall quality Abedi et al., 2021 [ 25 ] - Microbiology/Gut-microbiome PubMed, EMBASE, Web of Science, Scopus, Google Scholar, Open Grey, ProQuest Inception to 2021 Case–control, Cross-sectional, Cohort 32 - Blastocystis sp. infection Critically low Afari et al. 2014 [ 90 ] - Psychological Pubmed/MEDLINE, PsyINFO and Google Scholar 1948 to 2012 Case control. cohort 71 - Past history of reported trauma Critically low Almansour et al. 2024 [ 87 ] - Diet - Genetics - Environment - Pathology PubMed, Web of Science, CINAHL Ultimate, Scopus 2019 to 2024 Cross-sectional 52 - Food allergy - Family history - Smoking - Anxiety and depression - Low income - Workload - Occupation - Age - Stress - GERD - Diabetes Mellitus - Chronic disease - Abdominal pain Critically low Areeshi et al., 2013 [ 26 ] - Genetic Factors Medline, Embase Inception to 2013 Case–control 12 - Critically low Bernard et al. 2023 [ 86 ] - Pathological Pubmed, Cochrane, Embase Inception to 2023 Cohort, Case–control, Cross-sectional 10 - Spondyloarthropathy Critically low Chen et al., 2020 [ 28 ] - Dietary Factors PubMed, EMBASE, Web of Science Inception to 2019 Cross-sectional, Cohort 20 - High consumption of UPFs Low Chitkara et al., 2013 [ 29 ] - Socio-economic Factor - Physiology Medline, EMBASE 1966 to 2007 Observational 25 - Childhood living density of < 1 person per room - Childhood affluence (Hygiene hypothesis) - Birthweight < 1500 g during infancy - childhood sexual, physical, verbal and emotional abuse - Parental deprivation - social learning of illness behaviour Critically low Creed et al., 2019 [ 30 ] - Dietary Factors - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology Medline, Cochrane, Web of Science, 1998 to 2019 Cohort studies 38 - Female gender - Younger age - Psychological stressors, anxiety and depression - Gastrointestinal disorders (e.g. gastroenteritis) - Frequent use of healthcare - Pain disorders (including fibromyalgia and TMJ disorder) - sleep disorders - asthma - diabetes - migraine - chronic liver disease Critically low Czogalla et al., 2015 [ 31 ] - Genetic Factors PubMed Not Stated to Not Stated Case–control 12 previously published + 2 self-performed case controls - TNFSF15 rs4263839 Critically low El-Serag et al., 2009 [ 32 ] - Pathology Pubmed, Embase Inception to 2007 Cohort, Nested case–control 17 - GERD Critically low Fan et al., 2022 [ 33 ] - Microbiology/Gut-microbiome Medline, EMBASE, Web of Science, CINAHL 1967 to 2021 Case–control, Case Series 75 - Colonic Spirochaetosis spp. Critically low Ford et al., 2009 [ 34 ] - Microbiology/Gut-microbiome Medline, EMBASE 1950 to 2008 Case series, case–control 12 - Positive test for SIBO Critically low Gandhi et al., 2021 [ 35 ] - Microbiology/Gut-microbiome Medline, EMBASE 1966 to 2021 Case control, Cohort, Cross-sectional IBS: 15 IBS + IBD: 2 -Methane-positive SIBO (specifically IBS-C, not IBS-D) Low Guo et al., 2021 [ 36 ] - Pathology PubMed, EMBASE, Cochrane, Web of Science, Google Scholar, CINAHL Inception to 2020 Cross-sectional, Cohort, Case–control 6 - Restless legs syndrome Low Halvorson et al., 2006 [ 37 ] - Microbiology/Gut-microbiome Medline, Old Medline, Embase, Cochrane 1950 to 2005 Cohort 8 - Antecedent infectious gastroenteritis (IGE) Critically low Hawkings et al., 2023 [ 39 ] - Microbiology/Gut-microbiome PubMed, Medline, Scopus 2019 to 2023 Cross-sectional, Cohort, Case–control 45 - Previous SARS-CoV-2 infection Low Ibrahim, 2016 [ 40 ] - Dietary Factors - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology PubMed, Medline, Embase, Cochrane, Web of Science, Ovid, Google Scholar 1990 to 2015 Cross-sectional, Case–control 16 - Food hypersensitivity - Consumption of fatty food, obesity - Female medical students, - Family history of IBS, - Stress, anxiety, depression, sleep disorders Critically low Jiang et al., 2017 [ 41 ] - Genetic Factors PubMed, Embase, Science Direct, Chinese National Knowledge Infrastructure, Wanfang Inception to 2017 Case–control 11 Negative association: - C allele of GNβ3 C825T and IBS-C (C vs. T) Positive association: - IBS-D and CC genotype and IBS-D (CC vs. CT + TT) Critically low Joshee et al., 2022 [ 42 ] - Socio-economic Factor PubMed, EMBASE, Google Scholar, PsycINFO 1927 to 2020 Case–control, Cohort, Cross-sectional 15 - Adverse childhood experience in females with IBS Critically low Junaid et al. 2023 [ 85 ] - Psychological Medline, Embase, Web of science, Google scholar, Scopus 2001 to 2021 Case–control, Cross-sectional 7 - Childhood sexual abuse Critically low Keithlin et al., 2014 [ 43 ] - Microbiology/Gut-microbiome PubMed, Agricola, CabDirect, Food Safety and Technology Abstracts Inception to 2011 Observational 31 (of which 9 pertaining to IBS) - Critically low Kerkhoven et al., 2007 [ 72 ] - Genetic Factors Pubmed, Medline, Web of Science Inception to 2007 Case–control 8 - Critically low Kim et al., 2020 [ 44 ] - Microbiology/Gut-microbiome PubMed, Cochrane, Scopus, CINAHL Inception to 2019 Cross-sectional, Case–control 10 - Critically low Klem et al., 2017 [ 45 ] - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Physiology - Pathology Embase, Cochrane, Web of Science, Ovid 2006 to 2015 Cohort 45 - Female sex - Exposure to infectious enteritis - Depression - Somatisation at the time of infectious enteritis - Neuroticism - Abdominal pain - Diarrhoea for more than 7 days - Bloody stool - Antibiotic exposure at the time of PI-IBS - Paediatrics - Adults - Exposure to infectious enteritis, - Depression, somatisation at the time of infectious enteritis, neuroticism, - Abdominal pain, diarrhoea for more than 7 days, bloody stool, antibiotic exposure at the time of PI-IBS- Critically low Leech et al. 2018 [ 91 ] - Physiology Medline, Pubmed, Embase, AMED Inception to 2018 Case-contro, Cohort Cross-sectional 48 - Increased intestinal permeability Critically low Li et al., 2020 [ 46 ] - Microbiology/Gut-microbiome Pubmed, Medline, Embase, Cochrane Inception to 2019 Case–control 8 - Critically low Liu et al., 2022 [ 47 ] - Genetic Factors - Socio-economic Factors PubMed, Old Medline, Cochrane, Web of Science Inception to 2021 Cross-sectional surveys 11 - Female medical staff - Medical shift workers - Medical staff with poor sleep quality Low Lovell et al., 2012a [ 49 ] - Genetic Factors Medline, Embase, Embase Classical EMBASE Classic and EMBASE: 1947; MEDLINE: 1948 to 2011 Cross-sectional 55 - Female Critically low Lovell et al. 2012b [ 48 ] - Genetic Factors - Socio-economic Factor - Physiology Medline, Embase, Embase Classical 1947 to 2011 Cross-sectional surveys 81 - Female - Younger age below 50 Critically low Low et al., 2020 [ 50 ] - Dietary Factors - Genetic Factors - Environmental Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology Pubmed, Embase, Cochrane, Web of Science 1966 to 2018 Case–control, Cohort 27 - Food habits such as excessive intake of pepper - Alcoholism - Smoking - Shorter period of breast feeding - Parental reinforcement e.g. rejection, hostility, parental punishment, over interference, overprotection - Parental coping strategies e.g. family history of mental illness/alcohol - Substance use problems - Adults who have grown up with a father working in manual labour or in a home with living density of > 1 person per room - Child abuse (sexual, emotion, physical or psychological) - Adverse exposures e.g. history of dysentery, abdominal operation, overuse of antibiotics, exposure to coldness, fatigue - Raising herbivorous pets - Air pollution - Psychological distress during childhood e.g. parental history of anxiety/depression/somatisation - Family stress - Childhood parental deprivation - Introverted personality - Parental modelling of IBS symptoms e.g. history of IBS - Childhood gastrointestinal infections - Acute bacterial gastroenteritis - Children with mothers who were young (< 20), divorced or widowed, and with an education of 10–14 years - Children raised in affluent environment - Low birth weight - Preschoolers with a history of allergic disease Critically low Manzoli et al., 2017 [ 51 ] - Genetic Factors Medline, Scopus Inception to 2017 Cross-sectional 5 - Critically low Marasaco et al., 2023 [ 52 ] - Microbiology/Gut-microbiome Medline, EMBASE, Scopus Inception to 2022 Case–control 10 - Low Mathur et al., 2024 [ 53 ] - Genetic Factors - Environmental Factors - Microbiology/Gut-microbiome Medline, Cochrane, Web of Science, Scopus, Google Scholar 2019 to 2023 Case–control, Cohort 13 - Use of Rome III criteria compared to Rome IV criteria Critically low Motawea et al., 2023 [ 54 ] - Pathology PubMed, Web of Science, Scopus, Ovid Not stated to Not stated RCT, Cohort, Case–control, Cross-sectional 8 (of which 4 were included in meta-analysis) - IgM antibodies against GnRH and GnRH receptor Critically low Nastaskin et al., 2006 [ 55 ] - Pathology Medline, EMBASE, Cochrane, CINAHL, HEALTHSTAR, Evidence Based Medicine, Medscape EMBASE: 1980 Medline: 1966 HEALTHSTAR: 1975 CINAHL: 1982 Evidence-Based Medicine: 1991 Medscape: 1998 to EMBASE: 2006 Medline: 2006 HEALTHSTAR: 2004 CINAHL: 2006 Evidence-Based Medicine: 2004 Medscape: 2006 Cochrane Library: 2004 only RCT, Cross-sectional, Case–control 15 - Critically low Ng et al., 2018 [ 57 ] - Psychological Factors PubMed, Medline, EMBASE, Science Direct, Web of Science, Google Scholar, PsycINFO 1988 to 2018 Cohort, Case–control, Cross-sectional 8 - Post-traumatic stress disorder (PTSD) Critically low Ng et al., 2019 [ 56 ]  - Microbiology/Gut-microbiome Pubmed, Medline, Embase, Wanfang, Cochrane, Web of Science, Google Scholar 1960 to 2018 Case–control, Cross-sectional 13 - Helicobacter pylori ( H. pylori) infections in paediatric patients, - CagA-positive H. pylori Critically low Ng et al. 2024 [ 89 ] - Microbiology/Gut-microbiome - Environmental Medline, EMBASE, Scopus, Cochrane databases Inception to 2023 Case–control Cross-sectional, Ecological 7 - Air pollutants - Sharing a bedroom up to age 5 years old - Pet ownership; Owning a herbivorous pet - Gastroenteritis - Poor sanitation and hygiene - Gut dysbiosis Moderate Nikolova et al., 2022 [ 58 ] - Psychological Factors Medline, EMBASE, Google Scholar Inception to 2020 Cohort, Cross-sectional, Case–control 20 (of which 12 were used for quantitative analysis) - Depression Critically low Pan et al., 2014 [ 59 ] - Genetic Factors PubMed, EMBASE, Chinese National Knowledge Infrastructure, Cochrane, Ovid, Google Scholar Inception to 2013 Case–control 7 - Critically low Park et al., 2005 [ 60 ] - Pathology Medline 1966 to 2005 Experimental studies 12 - Food allergy caused by IgG4 and IgE-mediated hypersensitivity Critically low Pickett-Blakely, 2014 [ 61 ] - Physiology Medline, EMBASE 1980 to 2012 Cross-sectional, Case control, Case series 11 - Critically low Qin et al., 2013 [ 62 ] - Genetic Factors PubMed, EMBASE, Cochrane Inception to 2013 Case–control 8 Negative association: - IL-10 rs1800870 polymorphism (specifically Caucasian subgroup) Positive association: - IL-10 rs1800872 polymorphism (specifically Asian subgroup) Critically low Rostami et al., 2017 [ 63 ] - Microbiology/Gut-microbiome PubMed, ScienceDirect, Cochrane, Web of Science, Scopus Inception to 2017 Case–control Blastocystis : 17 D. fragilis : 4 - Blastocystis spp.. infections - Subtypes 1 and 3 of Blastocystis sp. Low Saha et al., 2022 [ 64 ] - Psychological Factors - Microbiology/Gut-microbiome - Physiology - Pathology Medline, Embase, Cochrane, Web of Science Inception to 2020 Cohort 13 - Higher BMI, - IBD - Infectious gastroenteritis, - Higher anxiety score and - C. difficile infection (CDI) symptom duration > 7 days Critically low Saidi et al. 2020 [ 65 ] - Pathology Pubmed, Embase, Web of Science Inception to 2019 Cohort, Case–control, Case cohort 13 - Endometriosis Critically low Schwille-Kiuntke et al., 2015 [ 66 ] - Pathology PubMed, Medline, Cochrane, Scopus, PsycINFO Not stated to Not stated Case–control, cohort study 6 - Traveller’s diarrhoea Critically Low Sibelli et al., 2016 [ 67 ] - Psychological Factors Medline, EMBASE, Web of Science, PsycINFO Inception to 2015 Cohort, Case–control 11 - Anxiety - Depression Critically low Sirri et al., 2017 [ 68 ] - Environmental Factors PubMed, Web of Science, Scopus Inception to 2016 Cross-sectional, Cohort, Case–control 42 - Critically low Silva et al. 2023 [ 84 ] - Microbiology/Gut-microbiome Pubmed, 2022 to 2023 Case–control, Cohort 8 - Covid 19 Critically low Stanculete et al., 2021 [ 69 ]  - Psychological Factors PubMed, Embase, Cochrane, Wiley Not stated to Not stated Cross-sectional, Cohort, Case–control 29 (4 of which pertain to IBS) - Critically low Svendsen et al., 2019 [ 70 ] - Microbiology/Gut-microbiome Medline, Embase 1966 (Medline) 1974 (Embase) to 2019 Cohort 34 - Campylobacter spp., - C. difficile , - Salmonella spp. - Shigella spp. - E. coli Critically low Tak et al. 2011 [ 92 ] - Physiology Medline, Embase, PsycINFO 1960 to 2009 Case–control 82 - Thabane et al., 2007 [ 71 ] - Microbiology/Gut-microbiome - Physiology Medline, EMBASE Medline: 1966 Embase: 1980 to 2007 Cohort, Case–Control 18 - Presence of intestinal infections - Shorter durations post-intestinal infection - Younger age Low Valencia et al., 2022 [ 2 ] - Genetic Factors - Physiology - Pathology PubMed, PMC, Medline, Cochrane 2017 to 2022 Case control, Narrative reviews, Systematic reviews, Cross-sectional, Cohort 23 - Female gender - Fibromyalgia - Increased expression of IL-1, IL-2, and TNF-a - Visceral hypersensitivity Critically low Vivien et al., 2021 [ 38 ] - Genetic Factors - Psychological Factors - Physiology - Pathology Pubmed, Medline, Embase, Web of Science Inception to 2021 Cohort, Cross-sectional, Case–control, Case Report, Interventional 36 - Obesity - Binge-eating disorder; eating disorder symptoms - Anorexia Nervosa, bulimia nervosa, EDNOS - Visceral hypersensitivity Low Wang et al., 2019 [ 73 ] - Microbiology/Gut-microbiome Medline, EMBASE, Cochrane, Web of Science, ClinicalTrials.gov Inception to 2018 Case–control 23 lower levels of: - Lactobacillus spp. - Bifidobacterium spp. Higher levels of: - E. coli - Enterobacteriaceae Low Wang et al. 2022a [ 74 ] - Microbiology/Gut-microbiome Pubmed, Embase, Cochrane Inception to 2019 Case–control 13 - H. pylori infection (in particular for IBS-D) Critically low Wang et al. 2022b [ 75 ]  - Socio-economic Factor Medline, EMBASE Inception to 2021 Case–control, Cohort, Cross-sectional 8 - Shift work schedule Critically low Wang et al. 2023 [ 76 ] - Microbiology/Gut-microbiome Pubmed, Embase, Cochrane, Web of Science, Scopus Inception to 2022 Cross-sectional, Longitudinal 12 - Critically low Wang et al. 2023 [ 88 ] - Microbiology/Gut-microbiome PubMed, EMBASE, Cochane library, Chinese National Knowledge 72023Infrastructure (CNKI), China Science and Technology Journal (VIP), Wanfang Inception to 2021 Case–control, Cross-sectional 31 - H. pylori Low Whitehead et al. 2002 [ 77 ] - Pathology - Psychological Factors Medline 1966 to 2002 Observational Not stated Comorbid somatic conditions: - fibromyalgia - chronic fatigue syndrome - chronic pelvic pain - TMJ disorder - interstitial cystitis - self-reported back pain - premenstrual syndrome - dysmenorrhea - dyspareunia - non-menstrual bleeding Comorbid psychiatric disorders: - major depressive disorder - anxiety - somatoform disorders Critically low Wongtrakul et al. 2022 [ 78 ] - Pathology Medline, EMBASE, Google Scholar Inception to 2020 Observational 11 - Development of migraine is associated with development of IBS Low Yang et al., 2022a [ 79 ] - Dietary Factors - Genetic Factors - Psychological Factors - Socio-economic Factor PubMed, Medline, EMBASE, Chinese, National Knowledge Infrastructure, CINAHL, Weipu, WANFANG Inception to 2021 Cross-sectional, Cohort 22 - Female gender - Post-graduate students - Medical majors - Smoking - Comorbidities: Anxiety, depression Critically low Yang et al., 2022b [ 27 ] - Pathology Medline, Chinese National Knowledge Infrastructure, Cochrane, Web of Science, Clinical Trial Inception to 2021 RCTs 12 - Vitamin D deficiency Low Zhang et al. 2014 [ 80 ] - Genetic Factors PubMed, EMBASE, Chinese National Knowledge Infrastructure, Web of Science Inception to 2013 Case–control 25 - Low Zhu et al. 2014 [ 81 ] - Genetic Factors - Socio-economic Factor - Physiology Medline, Embase, Embase Classical EMBASE Classic and EMBASE: 1947; MEDLINE: 1948 to 2013 Cross-sectional surveys 79 IBS prevalence - Females significantly more likely than males to develop IBS Developed vs. underdeveloped countries - Ratio of female to male prevalence of IBS significantly more in developed vs. underdeveloped countries Critically low Zhu et al. 2019 [ 82 ] - Genetic Factors PubMed, EMBASE, Cochrane, Web of Science, Clinical Trial 2000 to 2018 Case–control 28 Positive associations - SLC6A4 5-HTTLPR - TNFSF15 rs4263839 - TNFSF15 rs6478108 Negative associations: - COMT rs4680 - IL10 rs1800896 Low Zhuang et al. 2017 [ 83 ] - Microbiology/Gut-microbiome Pubmed, Chinese National Knowledge Infrastructure, Wanfang, Cochrane, Scopus, SinoMed, VIP Information Inception to 2015 Case–control 17 Chinese IBS patients - Bifidobacteria spp. - Lactobacillus spp. - E. coli - Enterobacteriaceae spp. Other regions comparison - Bifidobacteria spp. - Bacteroides spp. Critically low Legend: CFU  Colony-forming units, IBS  Irritable bowel syndrome, UPFs  Ultra-processed foods, SIBO  Small intestine bowel overgrowth, ACE  Adverse childhood experience, PI-IBS  Post-infectious irritable bowel syndrome, IBS-D  Irritable bowel syndrome with diarrhoea, IBS-C  Irritable bowel syndrome with constipation, IBS-M  Irritable bowel syndrome with mixed bowel habits, TMJ  temporomandibular joint, SMDs  Standardized mean difference, GnRH  Gonadotropin hormone-releasing hormone, GERD  Gastroesophageal reflux disease, PTSD  Post-traumatic stress disorder, SNPs  Single-nucleotide polymorphisms, COMT  Catechol-o-methyltransferase, CDI   Clostridioides difficile infection, Spp., Species, IGE  Infectious gastroenteritis, HDI  Health, Education and Income Indexes, ED  Eating disorder, EDNOS  Eating disorders not otherwise specified, BMI  Body mass index a Unless otherwise specified, factors refer to risk factors for IBS Summary of included reviews and their findings Case–control, Cross-sectional, Cohort - Diet - Genetics - Environment - Pathology PubMed, Web of Science, CINAHL Ultimate, Scopus - Food allergy - Family history - Smoking - Anxiety and depression - Low income - Workload - Occupation - Age - Stress - GERD - Diabetes Mellitus - Chronic disease - Abdominal pain Pubmed, Cochrane, Embase Cohort, Case–control, Cross-sectional - Socio-economic Factor - Physiology - Childhood living density of < 1 person per room - Childhood affluence (Hygiene hypothesis) - Birthweight < 1500 g during infancy - childhood sexual, physical, verbal and emotional abuse - Parental deprivation - social learning of illness behaviour - Dietary Factors - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology - Female gender - Younger age - Psychological stressors, anxiety and depression - Gastrointestinal disorders (e.g. gastroenteritis) - Frequent use of healthcare - Pain disorders (including fibromyalgia and TMJ disorder) - sleep disorders - asthma - diabetes - migraine - chronic liver disease IBS: 15 IBS + IBD: 2 - Dietary Factors - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology - Food hypersensitivity - Consumption of fatty food, obesity - Female medical students, - Family history of IBS, - Stress, anxiety, depression, sleep disorders Negative association: - C allele of GNβ3 C825T and IBS-C (C vs. T) Positive association: - IBS-D and CC genotype and IBS-D (CC vs. CT + TT) Medline, Embase, Web of science, Google scholar, Scopus Case–control, Cross-sectional - Genetic Factors - Environmental Factors - Psychological Factors - Microbiology/Gut-microbiome - Physiology - Pathology - Female sex - Exposure to infectious enteritis - Depression - Somatisation at the time of infectious enteritis - Neuroticism - Abdominal pain - Diarrhoea for more than 7 days - Bloody stool - Antibiotic exposure at the time of PI-IBS - Paediatrics - Adults - Exposure to infectious enteritis, - Depression, somatisation at the time of infectious enteritis, neuroticism, - Abdominal pain, diarrhoea for more than 7 days, bloody stool, antibiotic exposure at the time of PI-IBS- Medline, Pubmed, Embase, AMED Case-contro, Cohort Cross-sectional - Genetic Factors - Socio-economic Factors - Female medical staff - Medical shift workers - Medical staff with poor sleep quality - Genetic Factors - Socio-economic Factor - Physiology - Female - Younger age below 50 - Dietary Factors - Genetic Factors - Environmental Factors - Microbiology/Gut-microbiome - Socio-economic Factor - Physiology - Pathology - Food habits such as excessive intake of pepper - Alcoholism - Smoking - Shorter period of breast feeding - Parental reinforcement e.g. rejection, hostility, parental punishment, over interference, overprotection - Parental coping strategies e.g. family history of mental illness/alcohol - Substance use problems - Adults who have grown up with a father working in manual labour or in a home with living density of > 1 person per room - Child abuse (sexual, emotion, physical or psychological) - Adverse exposures e.g. history of dysentery, abdominal operation, overuse of antibiotics, exposure to coldness, fatigue - Raising herbivorous pets - Air pollution - Psychological distress during childhood e.g. parental history of anxiety/depression/somatisation - Family stress - Childhood parental deprivation - Introverted personality - Parental modelling of IBS symptoms e.g. history of IBS - Childhood gastrointestinal infections - Acute bacterial gastroenteritis - Children with mothers who were young (< 20), divorced or widowed, and with an education of 10–14 years - Children raised in affluent environment - Low birth weight - Preschoolers with a history of allergic disease - Genetic Factors - Environmental Factors - Microbiology/Gut-microbiome EMBASE: 1980 Medline: 1966 HEALTHSTAR: 1975 CINAHL: 1982 Evidence-Based Medicine: 1991 Medscape: 1998 to EMBASE: 2006 Medline: 2006 HEALTHSTAR: 2004 CINAHL: 2006 Evidence-Based Medicine: 2004 Medscape: 2006 Cochrane Library: 2004 only - Helicobacter pylori ( H. pylori) infections in paediatric patients, - CagA-positive H. pylori - Microbiology/Gut-microbiome - Environmental Medline, EMBASE, Scopus, Cochrane databases Case–control Cross-sectional, Ecological - Air pollutants - Sharing a bedroom up to age 5 years old - Pet ownership; Owning a herbivorous pet - Gastroenteritis - Poor sanitation and hygiene - Gut dysbiosis Negative association: - IL-10 rs1800870 polymorphism (specifically Caucasian subgroup) Positive association: - IL-10 rs1800872 polymorphism (specifically Asian subgroup) Blastocystis : 17 D. fragilis : 4 - Blastocystis spp.. infections - Subtypes 1 and 3 of Blastocystis sp. - Psychological Factors - Microbiology/Gut-microbiome - Physiology - Pathology - Higher BMI, - IBD - Infectious gastroenteritis, - Higher anxiety score and - C. difficile infection (CDI) symptom duration > 7 days - Anxiety - Depression Case–control, Cohort 29 (4 of which pertain to IBS) 1966 (Medline) 1974 (Embase) to 2019 - Campylobacter spp., - C. difficile , - Salmonella spp. - Shigella spp. - E. coli Medline, Embase, PsycINFO - Microbiology/Gut-microbiome - Physiology Medline: 1966 Embase: 1980 to 2007 Cohort, Case–Control - Presence of intestinal infections - Shorter durations post-intestinal infection - Younger age - Genetic Factors - Physiology - Pathology - Female gender - Fibromyalgia - Increased expression of IL-1, IL-2, and TNF-a - Visceral hypersensitivity - Genetic Factors - Psychological Factors - Physiology - Pathology - Obesity - Binge-eating disorder; eating disorder symptoms - Anorexia Nervosa, bulimia nervosa, EDNOS - Visceral hypersensitivity lower levels of: - Lactobacillus spp. - Bifidobacterium spp. Higher levels of: - E. coli - Enterobacteriaceae PubMed, EMBASE, Cochane library, Chinese National Knowledge 72023Infrastructure (CNKI), China Science and Technology Journal (VIP), Wanfang Case–control, Cross-sectional - Pathology - Psychological Factors Comorbid somatic conditions: - fibromyalgia - chronic fatigue syndrome - chronic pelvic pain - TMJ disorder - interstitial cystitis - self-reported back pain - premenstrual syndrome - dysmenorrhea - dyspareunia - non-menstrual bleeding Comorbid psychiatric disorders: - major depressive disorder - anxiety - somatoform disorders - Dietary Factors - Genetic Factors - Psychological Factors - Socio-economic Factor - Female gender - Post-graduate students - Medical majors - Smoking - Comorbidities: Anxiety, depression - Genetic Factors - Socio-economic Factor - Physiology IBS prevalence - Females significantly more likely than males to develop IBS Developed vs. underdeveloped countries - Ratio of female to male prevalence of IBS significantly more in developed vs. underdeveloped countries Positive associations - SLC6A4 5-HTTLPR - TNFSF15 rs4263839 - TNFSF15 rs6478108 Negative associations: - COMT rs4680 - IL10 rs1800896 Chinese IBS patients - Bifidobacteria spp. - Lactobacillus spp. - E. coli - Enterobacteriaceae spp. Other regions comparison - Bifidobacteria spp. - Bacteroides spp. Legend: CFU  Colony-forming units, IBS  Irritable bowel syndrome, UPFs  Ultra-processed foods, SIBO  Small intestine bowel overgrowth, ACE  Adverse childhood experience, PI-IBS  Post-infectious irritable bowel syndrome, IBS-D  Irritable bowel syndrome with diarrhoea, IBS-C  Irritable bowel syndrome with constipation, IBS-M  Irritable bowel syndrome with mixed bowel habits, TMJ  temporomandibular joint, SMDs  Standardized mean difference, GnRH  Gonadotropin hormone-releasing hormone, GERD  Gastroesophageal reflux disease, PTSD  Post-traumatic stress disorder, SNPs  Single-nucleotide polymorphisms, COMT  Catechol-o-methyltransferase, CDI   Clostridioides difficile infection, Spp., Species, IGE  Infectious gastroenteritis, HDI  Health, Education and Income Indexes, ED  Eating disorder, EDNOS  Eating disorders not otherwise specified, BMI  Body mass index a Unless otherwise specified, factors refer to risk factors for IBS High ultra-processed food consumption [ 28 ] and fatty food [ 40 ] were reported as significantly associated with IBS development. Alcohol consumption [ 30 , 50 , 79 ] were reported as risk factors of IBS. Food allergy [ 87 ] was also reported as a common risk factor. Genetic factors are being female [ 2 , 30 , 40 , 45 , 47 – 49 , 51 , 79 , 81 ], having a family history of IBS [ 49 , 50 , 87 ] and TNFSF15 polymorphism [ 82 ]. Conflicting evidence surrounds 5HTTLPR as most studies [ 26 , 72 , 80 ] did not report it as a risk factor, the SLC6A4 [ 82 ] polymorphism is significantly associated with IBS development. GNB3 C825T [ 41 , 59 , 82 ], IL-10 rs1800871 [ 62 , 82 ], IL-10 rs1800870 [ 62 ], IL-10 rs1800872 [ 62 ] and TNF-α rs1800629 [ 82 ] polymorphisms were found not to be risk factors for IBS. Conversely, COMT rs4680 [ 82 ] and IL-10 rs1800896 [ 82 ] were found to be significantly associated with decreased IBS development. Smoking [ 87 ], air pollutants [ 50 , 89 ], sharing a bedroom up to age 5 years old [ 89 ], raising herbivorous pets [ 50 , 89 ] or history of pet ownership [ 89 ], poor sanitation [ 89 ] and shorter period of breastfeeding [ 50 ] were found to have significant association with IBS development. Anxiety disorders [ 30 , 40 , 45 , 67 , 79 , 87 ], depression [ 30 , 40 , 45 , 58 , 67 , 79 , 87 ], neuroticism [ 45 ], somatization at the time of infectious enteritis [ 45 ], stress [ 30 , 40 , 87 ], binge-eating disorder, anorexia nervosa and eating disorders not otherwise specified [ 38 ] were found to have significant association with IBS development. Post-traumatic stress disorder (PTSD) [ 57 ], history of past trauma [ 90 ] and history of childhood sexual abuse [ 85 ] were found to be a significant risk factor of IBS. Clostridioides difficile (C. difficile) [ 64 ] infection for longer than 7 days was found to be a significant risk factor for IBS. A history of colonic spirochetosis [ 33 ], antibiotic exposure [ 45 , 50 ], infective gastroenteritis [ 30 , 37 , 45 , 50 , 71 , 89 ], Blastocystis spp. [ 63 , 73 ], C. difficile , Salmonella spp., Shigella spp., Escherichia coli (E. coli) [ 70 ] and Helicobacter pylori [ 88 ] were found to have significant associations with IBS development. Levels of Bifidobacterium spp. [ 73 , 83 ] were reported to be significantly lower in patients with IBS compared to patients without IBS. Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) was also associated with a higher incidence of IBS [ 53 ]. A significant proportion of the IBS population was also observed to have gut dysbiosis [ 89 ]. Child abuse, childhood living density of less than one person per room, parental deprivation, childhood affluence [ 29 , 50 ], social learning of illness behaviours, parental reinforcement (rejection, hostility, parental punishment, over interference, overprotection), parental coping strategies (family history of mental illness/alcohol, substance use problems), psychological distress during childhood (e.g. parental history of anxiety/ depression/somatization, family stress, childhood, introverted personality) and children with mothers who were young (less than 20 years old), divorced or widowed, and with an education of 10 to 14 years [ 50 ] were reported as risk factors of IBS. Shift work [ 47 , 74 ], students in medical majors [ 40 , 79 ], postgraduate students [ 79 ], poor sleep quality [ 47 ] and frequent use of healthcare [ 30 ] had significant associations with IBS development. High workload, low income and occupation types were commonly reported features of IBS populations [ 87 ]. Low birth weight [ 29 , 50 ] and increased intestinal permeability [ 91 ] were found to have significant positive association with IBS. There is inconclusive evidence of increasing age [ 2 , 30 , 45 , 48 , 71 , 81 , 87 ] as a risk factor for IBS. Gastroesophageal reflux disease (GERD) [ 32 , 55 , 87 ], migraine [ 30 , 78 ], vitamin D deficiency [ 79 ], the presence of IgM antibodies against gonadotropin hormone-releasing hormone (GnRH) and GnRH receptor [ 54 ], preschoolers with a history of atopy/allergy [ 50 ], women with endometriosis [ 65 ], asthma [ 30 ], diabetes [ 30 , 87 ], previous abdominal operation and exposure to coldness and fatigue [ 50 ] were found to be significant risk factors for IBS development. Temporomandibular joint (TMJ) disorder [ 30 , 77 ], fibromyalgia syndrome [ 2 , 30 , 77 ], visceral hypersensitivity [ 2 , 38 ], food hypersensitivity [ 40 , 60 ], sleep disorders [ 30 , 40 ], spondyloarthropathy [ 86 ], chronic liver disease [ 30 ], a history of dysentery [ 45 ], restless leg syndrome [ 36 ], having diarrhoea for more than 7 days [ 45 ] and abdominal pain [ 45 , 87 ] had a significant association with IBS development. A history of chronic disease was also reported as a common risk factor for IBS development [ 87 ]. Amongst the risk factors mentioned, female gender, anxiety disorder, depression and gastroenteritis were the most frequently mentioned across reviews. Depression and gastroenteritis were supported with relatively higher evidence, with a “moderate score” when assessed using GRADE. Depression had an association magnitude ranging from RR 1.90 to RR 5.57 and OR 1.49 to OR 2.15, while gastroenteritis had an association with magnitude of RR 3.8 and OR 5.86 to OR 7.3 reported. Female gender and anxiety disorder were supported by relatively lower levels of evidence when assessed by grade, with a “low” score attributed to both. Across reviews, female gender had an association of magnitude OR 1.36 to OR 2.29 while anxiety disorder has an association magnitude of RR 2.38 and OR 1.97 to 2.35. The results of GRADE evaluation for the aforementioned factors are summarized in Table  3 . Table 3 Summary of the main findings as per GRADE Outcome Risk of bias Inconsistency Indirectness Imprecision Publication Bias Absolute effect Overall certainty (GRADE) Female Gender High—Many reviews are of “low” or “critically low” quality (AMSTAR2 assessment) Moderate—Some variability in reported associations Low—Directly addresses IBS development in relevant populations Moderate—Some studies have wide confidence intervals, but the overall association remains significant Not assessed Female gender shows a higher likelihood of IBS Low ⨁⨁◯◯ Anxiety Disorder High—Many reviews are of “low” or “critically low” quality (AMSTAR2 assessment) Moderate—Some variability in reported associations Low—Directly addresses IBS development in relevant populations Moderate—Some studies have wide confidence intervals, but the overall association remains significant Not assessed Anxiety disorder is associated with an increased risk of IBS Low ⨁⨁◯◯ Depression High—Many reviews are of “low” or “critically low” quality (AMSTAR2 assessment) Moderate—Some variability in reported associations Low—Directly addresses IBS development in relevant populations Moderate—Some studies have wide confidence intervals, but the overall association remains significant Not assessed Depression is associated with an increased risk of IBS Moderate ⨁⨁⨁◯ Gastroenteritis High—Many reviews are of “low” or “critically low” quality (AMSTAR2 assessment) Low—Consistent association across studies for post-infectious IBS Low—Directly addresses IBS development in relevant populations Moderate—Some studies have wide confidence intervals, but the overall association remains significant Not assessed Gastroenteritis is associated with PI-IBS with approximately 10% prevalence in affected patients Moderate ⨁⨁⨁◯ Summary of the main findings as per GRADE Low ⨁⨁◯◯ Low ⨁⨁◯◯ Moderate ⨁⨁⨁◯ Moderate ⨁⨁⨁◯

Irritable bowel syndrome (IBS) is a disorder of the gut-brain axis diagnosed through the symptom cluster outlined in the ROME IV criteria [ 1 , 2 ]. It is an exceedingly common condition, affecting some 4–9% [ 3 ] of the global population, and with significant adverse effects and impediments. Research has consistently shown that IBS reduces the quality of life related to health [ 4 ] and contributes to workplace absenteeism at a societal level [ 5 ], underlining its economic burden [ 6 ]. Additionally, the global trend towards adopting a Western diet and lifestyle [ 7 ] is expected to increase the incidence of IBS. Given its rising prevalence [ 7 ] and the chronic nature of this condition [ 8 ], this necessitates further research into the risk factors for new-onset IBS to develop preventive measures against the onset of the condition. At present, the causes of IBS are varied, complex, and incompletely understood [ 9 ]. Research continues to explore a broad range of risk factors, including genetic [ 10 ], immunological [ 11 ], psychological [ 12 ], and dietary elements [ 13 ]. Recent years have seen burgeoning interest in understanding how the gut microbiota [ 14 ], the interactions between the gut and the brain [ 15 ], and gastrointestinal motility [ 16 ] contribute to the development of IBS. Furthermore, the field of exposomics [ 17 , 18 ], which examines the influence of environmental factors on disease development, is shedding new light on new risk factors for IBS. For instance, air pollution, already linked to various health issues, is now being investigated for its potential role in altering the gut microbiome and increasing the risk of IBS in previously healthy individuals [ 19 , 20 ]. The expanding body of research underscores the relevance and timeliness of an overview of systematic reviews on these topics, which would help synthesize and critique current knowledge and findings. Addressing this gap, this study attempts a umbrella review of existing systematic reviews [ 21 ], specifically focusing on risk factors associated with the onset of IBS in individuals who were previously healthy. These findings aim to bridge the gap between research on IBS risk factors and their applications in clinical settings, enhance current preventive strategies, and inspire further investigations into this critical area.

This review of reviews provides an overview of the current evidence regarding the risk factors for the IBS development. Eight overarching categories of risk factors were identified across the 69 included systematic reviews in this study, as illustrated in Fig.  2 . Amongst the various risk factors mentioned, four were frequently identified across the included reviews, supported by robust evidence for its position as a risk factor of IBS development: female gender, anxiety disorder, depression and gastroenteritis. Fig. 2 Overview of risk factors for IBS development based on existing systematic reviews Overview of risk factors for IBS development based on existing systematic reviews IBS has long been associated with female gender, with an estimated 2–2.5:1 male-to-female ratio for IBS development [ 93 ]. While the exact pathophysiology has not been ascertained, a common mechanistic pathway emphasized across literature are the hormonal differences between both genders [ 94 ]. In addition to the modulatory effect of progesterone on the 5-hydroxytrptamine (5-HT) system that controls peristalsis [ 95 ], estrogen and progesterone have an inhibitory effect on smooth muscle contraction [ 94 ]. Consequently, IBS, especially the constipation variant (IBS-C), has a higher incidence in women compared to men [ 96 ]. While the interplay between gender and IBS development highlights the importance of this risk factor, the association with worse outcomes further compels further effort in preventing IBS development within this patient group. Fan et al. reports higher IBS symptoms score and lower IBS-quality of life (IBS-QOL) scores experienced in female patients [ 97 ]. Cain et al. also reports more somatic symptoms experienced by women afflicted with IBS, including joint and muscle pain [ 98 ]. However, despite worse outcomes in female populations, abdominal concerns are more likely to be minimized by healthcare professionals [ 99 ]. Windrim et al. reports the internalization of normative views regarding women’s pain of lower concern as a possible explanation. Given its significance as a risk factor and outcome modulator, further emphasis on this risk factor is necessitated in clinical guidelines aimed at prevention of IBS development. A bi-directional association has been established between both mental conditions and IBS development [ 45 , 100 ]. Mechanistically, two pathways have been described. The increased release of corticotropin-releasing hormone (CRH) in response to stress [ 12 ] in anxiety and depression causes hyperactivation of the hypothalamic–pituitary–adrenal axis and autonomic nervous system, consequently altering gut motility and increasing visceral sensitivity [ 101 ]. Stress-induced microbiota dysbiosis also causes gut barrier dysfunction and immune activation, further contributing to gut motility abnormalities [ 102 ]. The impact of IBS onset on individuals with anxiety and depression is extensive, as they are more likely to experience reduced quality of life from the symptoms of IBS and exhibit reduced treatment adherence compared to those without anxiety or depression [ 100 , 103 ]. However, patients with undiagnosed anxiety and depression who display symptoms of IBS are only offered central neuromodulators and psychological therapies when they fail to respond to pharmacotherapy for symptomatic management of IBS [ 104 ]. The resultant delay in resolution of IBS symptoms may cause patient dissatisfaction and inadvertently lead patients to seek alternative therapies which lack robust evidence, thereby increasing the risk of harm [ 102 ]. This underscores the need for more stringent screening of comorbid anxiety and depression disorders in the diagnosis of IBS to allow for accurate choice of pharmacotherapies and early referral for psychotherapies where required [ 105 , 106 ]. In agreement with literature, acute gastroenteritis is a common risk factor amongst various systematic reviews, with reports approximating 10% pooled prevalence [ 107 ] of post-infectious IBS (PI-IBS) in acute gastroenteritis patients. Although the exact mechanism is poorly understood, common pathophysiological hypotheses include prolonged imbalance of host immune cells and mediators that affect inflammatory homeostasis, disruption to the intestinal mucosal barrier and intestinal dysbiosis [ 108 ]. While any pathogens may potentiate PI-IBS, notable pathogens strongly associated with PI-IBS include as follows: Norovirus [ 109 ] and Rotavirus [ 110 ], E. coli [ 111 ], Salmonella spp. [ 112 ], Campylobacter spp. and Giardia duodenalis ( G. duodenalis) [ 113 ]. Despite being a common risk factor, gastroenteritis is however, an easily treatable cause of IBS development. Epidemiological data would prove crucial in capitalizing on this information for effective prevention and treatment considering inter-region difference in infective gastroenteritis pathogen. In addition to gastroenteritis, a patient’s gut microbiota also plays a role in IBS development. Specifically, changes in prevalence of indigenous species such as Faecalibacterium spp., Lactobacillus spp. and Bifidobacteria spp. have been linked to IBS development [ 73 , 114 ]. As probiotics can modulate the composition of gut microbiota, this has resulted in the recent interest for probiotic trials of IBS relief observed in literature [ 115 , 116 ]. Based on the findings of this study, the authors of this study suggest that future systematic reviews on this topic strongly adhere to the tenets of systematic reviews as outlined by PRISMA-P guidelines. In particular, item 16b and accounting for the biases in the discussion (part of 23b) are requirements that current reviews tend not to fulfill. Furthermore, other requirements, such as 14, 18 and 24a-c, were only partially met. This may be attributed to the multi-faceted nature of the requirement. Future studies should take more care in adequately addressing these criteria. To ensure quality of published literature, it is advised that journals actively require a protocol checklist, ideally the PRISMA-P checklist, to be submitted for peer review. In agreement with the current stance on study quality [ 117 ], adherence to such reporting standards should also have more weightage in a journal’s consideration for publication of the report. To the author’s best knowledge, this study presents the first review of reviews to investigate the current evidence of risk factors for IBS development. The findings from this study were reported according to replicable methodology, which adhered to the PRISMA guidelines for systematic reviews [ 22 ], recent recommendations by Gates et al. [ 118 ] and published literature. The authors of this study also acknowledge the current limitations of this review. Review of reviews focus on published systematic reviews and meta-analyses; thus, more recent studies not identified in original reviews may not have been included in this umbrella review. Secondly, a loss of granularity is apparent in some of the findings listed above, for example the lack of clarity regarding the dose response of specific risk factors including air pollution. Lastly, the evaluation of article quality reveals low adherence to professionally accepted guidelines in several of the systematic reviews and meta-analyses reviewed. When evaluated holistically using the GRADE evaluation model, the evidence ranged between low to moderate for the major risk factors identified in this review. In view of the current limitations, the authors of this review urge the readers to interpret the presented findings with caution.

This umbrella review identified eight overarching categories of risk factors for IBS, of which female gender, anxiety, depression and gastroenteritis were supported by comparatively more robust evidence. While this review attempts to further the understanding regarding the significant risk factors for the development of IBS and the current evidence landscape, the multi-factorial nature of IBS demands continued research. Given that several reviews did not satisfy the good practices and recommendations for methodology as outlined by the PRISMA guidelines [ 22 ], there is also a need for caution when interpreting the data contained within the current reviews. The findings of this study also urge stronger adherence to established guidelines for the methodology of future research conducted in this area.

Supplementary Material 1. Supplementary Material 1.