---
title: "Risk of Systemic Rheumatic Diseases in People with Irritable Bowel Syndrome — Article Content Not"
id: "frontiers-in-immunology-17-risk-of-systemic-rheumatic-diseases-in-people-with-irritable-bowel-syndrome-a"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-17-risk-of-systemic-rheumatic-diseases-in-people-with-irritable-bowel-syndrome-a"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1779191"
published_at: "2026-08-03T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Risk of Systemic Rheumatic Diseases in People with Irritable Bowel Syndrome — Article Content Not
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-17-risk-of-systemic-rheumatic-diseases-in-people-with-irritable-bowel-syndrome-a
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1779191)
- **Published At:** 2026-08-03T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The provided source page did not include the article text or study data for the paper titled “Risk of systemic rheumatic diseases in people with irritable bowel syndrome: a global-federated cohort analysis.” - Key study elements such as the **cohort characteristics**, data sources, analytic methods, inclusion/exclusion criteria, follow-up duration, and statistical outcomes were not present on the retrieved page. - No reported estimates, effect sizes, hazard ratios, confidence intervals, or p-values were available from the source to support any association between **irritable bowel syndrome** and **systemic rheumatic diseases**. - Information on which specific **systemic rheumatic diseases** were evaluated (for example, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, etc.) was not provided in the source content. - Study design details — including how a “global-federated” approach was implemented, participating registries or institutions, data harmonization procedures, privacy-preserving methods, or validation steps — were not reported on the retrieved page. - The source did not provide author names, affiliations, funding sources, conflicts of interest, or peer review and publication metadata for the study beyond site navigation elements. - Because primary results and methods were missing, clinical interpretation, applicability, and quality assessment (risk of bias, confounding control, sensitivity analyses) cannot be performed from the retrieved content. - Users seeking the study’s findings should consult the full article on the journal site or contact the publisher; the retrieved page appears to include only journal navigation and not the article body itself.
## Clinical Analysis & Structured Key Points
Frontiers | Risk of systemic rheumatic diseases in people with irritable bowel syndrome: a global-federated cohort analysis ORIGINAL RESEARCH article Front. Immunol. , 03 August 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1779191 Published in Frontiers in Immunology Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders 7 impact factor 11.3 citescore Part of a Research Topic Big data research, precision medicine and real‑world evidence in autoimmune and rheumatic diseases 46k views 22 articles Editor & Reviewers Edited by Y M Yao Min Hung Reviewed by O K Ozgur Kasapcopur Y C Yen-Yang Chen P W Philip W. Voorneveld Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 Baseline demographic and clinical characteristics of patients with and without irritable bowel syndrome before and after 1:1 propensity score matching. View in article Table 2 Age-stratified associations between irritable bowel syndrome and incident systemic rheumatic diseases in adults aged 18–49 years after propensity score matching. View in article Table 3 Age-stratified associations between irritable bowel syndrome and incident systemic rheumatic diseases in adults aged 50-65 years after propensity score matching. View in article Table 4 Sex-stratified associations between irritable bowel syndrome and incident systemic rheumatic diseases after propensity score matching. View in article ORIGINAL RESEARCH article Front. Immunol. , 03 August 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1779191 Risk of systemic rheumatic diseases in people with irritable bowel syndrome: a global-federated cohort analysis S G Shuo-Yan Gau 1,2,3 † Y S Yu-Jung Su 4 † S Y Shih-Chi Yang 5 C C Chien-Chin Chen 6,7,8,9 S C Solomon Chih-Cheng Chen 10,11 H C Hui-Chin Chang 12,13,14 * M W Meng-Che Wu 14,15,16 * 1. Department of Medical Education, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan 2. Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany 3. Department and Graduate Institute of Business Administration, National Taiwan University, Taipei, Taiwan 4. Orthopedics Department, Chi-Mei Medical Center, Tainan, Taiwan 5. Education Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 6. Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan 7. Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan 8. Ph.D. Program in Translational Medicine, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 9. Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan 10. Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan 11. Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei, Taiwan 12. Evidence-based Medicine Center, Chung Shan Medical University Hospital, Taichung, Taiwan 13. Library, Chung Shan Medical University Hospital, Taichung, Taiwan 14. School of Medicine, Chung Shan Medical University, Taichung, Taiwan 15. Division of Pediatric Gastroenterology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan 16. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan See more Article metrics View details Abstract Background: Irritable bowel syndrome (IBS) is a prevalent disorder of gut–brain interaction increasingly linked to immune and inflammatory dysregulation. Whether IBS predisposes to systemic rheumatic diseases remains uncertain. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which integrates anonymized electronic health records from more than 150 healthcare organizations and 150 million patients worldwide. Adults (≥18 years) diagnosed with IBS (≥2 visits) between 2015 and 2023 were compared with matched controls undergoing routine health evaluations without IBS. Exclusion criteria included malignancy, pre-existing systemic rheumatic diseases, and death before the index date. Propensity score matching (1:1) balanced demographics, comorbidities, psychiatric disorders, and socioeconomic factors. The primary outcome was incident systemic rheumatic disease, categorized into inflammatory arthritis (ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, gout) and connective tissue disorders (systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, dermatomyositis/polymyositis). Risk estimates were generated using the TriNetX analytic function, reporting hazard ratios with 95% confidence intervals. Sensitivity analyses included alternative definitions, extended washout periods (24 and 36 months), varying follow-up durations, active comparator cohorts, and negative controls. Cross-dataset validation was performed using the TriNetX US Collaborative Network. Results: After matching, 459966 patients were included in each cohort. Irritable bowel syndrome was associated with increased risks of ankylosing spondylitis (HR 2.57, 95% CI 2.22–2.98), psoriatic arthritis (HR 2.03, 95% CI 1.80–2.29), rheumatoid arthritis (HR 1.42, 95% CI 1.28–1.56), and gout (HR 1.34, 95% CI 1.27–1.42). Elevated risks were also observed for systemic lupus erythematosus (HR 1.84, 95% CI 1.65–2.04), Sjögren syndrome (HR 2.84, 95% CI 2.60–3.12), systemic sclerosis (HR 2.09, 95% CI 1.64–2.67), and dermatomyositis (HR 1.52, 95% CI 1.11–2.07). These associations remained across multiple sensitivity and stratified analyses. Conclusions: IBS was associated with a higher risk of diverse systemic rheumatic diseases. Further studies are warranted to clarify the mechanisms underlying these observed associations. Introduction Irritable bowel syndrome (IBS) is a common disorder of gut–brain interaction characterized by recurrent abdominal pain associated with altered bowel habits in the absence of structural disease. It is diagnosed according to symptom-based criteria, such as the Rome framework ( 1 ). Population-based surveys indicate that IBS affects approximately 10% of the global population, with a substantial female predominance and considerable regional variability ( 2 ). Beyond gastrointestinal symptoms, IBS is associated with impaired health-related quality of life and substantial indirect costs related to work absenteeism and presenteeism ( 3 , 4 ). Accumulating evidence suggests that IBS frequently coexists with immune-mediated and rheumatic conditions ( 5 – 7 ). Population-based studies have reported a higher risk of IBS among individuals with atopy, autoimmune diseases, and other chronic immune disorders than among community controls ( 8 , 9 ). In patients with systemic lupus erythematosus (SLE), IBS-like symptoms are common and are associated with poorer quality of life and greater fatigue, suggesting overlapping pathophysiological mechanisms involving functional bowel symptoms and immune-mediated inflammatory pathways ( 10 ). Furthermore, recent evidence has documented an increased burden of IBS among patients with spondyloarthritis, underscoring clinically relevant gut–joint interactions ( 11 ). Despite these observations, the temporal association between IBS and subsequent systemic rheumatic diseases remains incompletely characterized. Most prior studies have evaluated IBS-type symptoms in patients with established rheumatic diseases or have focused on selected conditions such as rheumatoid arthritis (RA), SLE, or spondyloarthritis ( 8 , 11 ). Recent evidence has also highlighted that rheumatologic comorbidities are more commonly observed in patients with inflammatory conditions such as inflammatory bowel disease (IBD), suggesting a potential link between chronic inflammation and systemic rheumatic manifestations ( 12 ); however, whether a similar association exists for IBS, which lacks overt inflammatory pathology, remains unclear. Less is known about whether individuals diagnosed with IBS subsequently experience a higher risk of a broader range of systemic rheumatic diseases in routine clinical practice. This question is clinically relevant because symptoms attributed to IBS may coexist with nonspecific systemic manifestations, while delayed recognition of rheumatic diseases may adversely affect long-term outcomes. Therefore, we conducted a large-scale retrospective cohort study using the TriNetX Global Collaborative Network. The primary objective was to examine the association between IBS and incident systemic rheumatic diseases, covering both inflammatory arthritis and connective tissue disease categories. We further evaluated the consistency of these associations through alternative IBS definitions, extended washout periods, active comparator cohorts, negative-control outcomes, subgroup analyses, and cross-dataset validation. Materials and methods Study design and data source We conducted a retrospective cohort study using real-world data from the TriNetX Global Collaborative Network. This international research platform aggregates continually updated, anonymized electronic health records (EHRs) from more than 150 participating healthcare organizations across multiple continents, representing a patient population of over 150 million individuals. TriNetX has been widely used in previous epidemiological, health economics, and outcomes research ( 13 – 15 ). Cohort definition The study cohorts were defined using specific diagnostic, procedural, and medication codes (detailed in Supplementary Table 1 ) recorded between 2015 and 2023. The IBS cohort comprised patients with a documented diagnosis of IBS who had attended at least two healthcare visits. The control cohort consisted of adults undergoing routine health evaluations with no documented diagnosis of IBS. Exclusion criteria included age younger than 18 years, any diagnosis of inflammatory bowel disease, a history of malignancy, pre-existing systemic rheumatic disease, or death before the index date. Individuals with inflammatory bowel disease were excluded regardless of the timing of diagnosis to minimize potential disease overlap and diagnostic ambiguity. Outcomes The primary outcomes were incident systemic rheumatic diseases recorded after the index date. These outcomes were grouped into inflammatory arthritis and connective tissue disease categories. Inflammatory arthritis outcomes included ankylosing spondylitis, RA, psoriatic arthritis, and gout. Connective tissue disease outcomes included SLE, Sjögren syndrome, systemic sclerosis, and dermatomyositis/polymyositis. The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes used for exposure, outcomes, covariates, and sensitivity analyses are provided in Supplementary Table 1 . Covariates and propensity score matching To improve baseline comparability, IBS patients and controls underwent 1:1 propensity score matching. Matching was performed using greedy nearest-neighbor matching without replacement and a caliper of 0.10 pooled standard deviations. The propensity score model included age, sex, race, body mass index, hypertension, hyperlipidemia, diabetes mellitus, psychiatric conditions coded within ICD-10-CM F40–F48, and mental or behavioral disorders related to psychoactive substance use coded within F10–F19. Medication exposure was reported descriptively in the baseline table but was not included in the primary propensity score model. Covariate balance was assessed using standardized mean differences, with an absolute value below 0.1 considered acceptable. Body mass index was operationalized as a binary variable indicating a recorded value of at least 25 kg/m². Missing BMI values were not imputed. Patients with unavailable race information were retained within the platform-defined “unknown race” category. Sensitivity and comparator analyses Several sensitivity analyses were performed to examine the consistency of the findings ( Supplementary Table 2 ). Alternative IBS definitions were applied, including repeated IBS diagnosis within 30 days, more than five IBS diagnostic records, IBS with abdominal pain, and IBS with change in bowel habit. Additional models used shorter follow-up windows and extended washout periods of 24 and 36 months. To address potential diagnostic ambiguity from other gastrointestinal disorders, additional analyses excluded individuals with a history of cholecystectomy or selected abdominal disorders that may mimic IBS. These disorders included celiac disease, microscopic colitis, diseases of the esophagus, stomach, and duodenum, and diseases of the peritoneum and retroperitoneum. Active comparator analyses were performed using patients with hernia and patients with gastritis or duodenitis as alternative control groups. The gastritis or duodenitis comparator was used as a gastrointestinal healthcare-seeking comparison group rather than as a true negative-control exposure. Negative-control outcome analyses were conducted using tuberculosis and rickettsioses. To further address differential healthcare utilization, an additional propensity score model included platform-defined visit variables. These variables consisted of any prior ambulatory visit and any prior inpatient encounter recorded in TriNetX. They were assessed using all available pre-index records through the day before the index date and were not based on specific diagnostic or procedural codes. The TriNetX interface did not provide visit counts, specialty-specific encounter information, referral patterns, or laboratory testing intensity. Subgroup analyses Subgroup analyses were performed according to age, sex, and race. Propensity score matching was repeated separately within each sensitivity and stratified analysis. Statistical analysis All statistical analyses were performed within the “compare outcomes” module of the TriNetX analytic platform. Information regarding data access and analysis date were presented in the Supplementary statement. Time-to-event outcomes were evaluated using the built-in TriNetX survival analysis module, which generated hazard ratios (HR) with 95% confidence intervals (95% CI), Kaplan–Meier estimates, and log-rank p values. Risk ratios and risk differences were also reported for the primary analysis to provide absolute risk context. The underlying model specification was not accessible to investigators, and formal testing of the proportional hazards assumption was unavailable in the present analysis. Individual-level censoring dates and details of the censoring algorithm were likewise unavailable through the federated interface. No formal a priori power calculation was performed because this retrospective database study included all eligible patients identified through the TriNetX Global Collaborative Network according to prespecified criteria. The TriNetX federated interface did not provide a dedicated power-analysis function or individual-level data access required for an independent formal time-to-event power calculation. Statistical precision was therefore assessed using observed event counts and 95% confidence intervals, and absolute risk measures were reported to aid interpretation. Death recorded before the index date was treated as an exclusion criterion. Death occurring during follow-up was not incorporated as a competing event, and no competing-risk analysis was performed. Continuous variables were reported as mean ± standard deviation when available from the TriNetX output. Categorical variables were presented as number followed by percentage. Baseline covariate balance after propensity score matching was assessed using standardized mean differences rather than parametric or nonparametric hypothesis tests, with an absolute value below 0.1 considered acceptable. Ethical approval Access to the Global Collaborative Network was utilized for this research. The study adhered to the ethical stipulations outlined in the Declaration of Helsinki and was granted a waiver of informed consent by the Institutional Review Board of Ditmanson Medical Foundation Chia-Yi Christian Hospital (IRB No. IRB2025121). Results Study population and baseline characteristics From 156,615,696 adults in the TriNetX Global Collaborative Network, 459,966 individuals with IBS and 6,283,812 individuals without IBS met the eligibility criteria. After 1:1 propensity score matching, 459,966 patients were retained in each cohort for the primary analysis ( Figure 1 ). Figure 1 Flowchart of patient selection and cohort construction. Flowchart showing the identification of eligible adults from the TriNetX Global Collaborative Network between 2015 and 2023. Patients with irritable bowel syndrome (IBS) and individuals without a recorded IBS diagnosis were screened according to predefined inclusion and exclusion criteria. Individuals younger than 18 years or with inflammatory bowel disease, malignancy, pre-existing systemic rheumatic disease, or death before the index date were excluded. After 1:1 propensity score matching, 459,966 patients were retained in each cohort for the primary analysis. Before matching, patients with IBS were more often female and White, and they had higher frequencies of anxiety-related disorders and selective serotonin reuptake inhibitor use. After matching, most baseline characteristics were well balanced between cohorts, with only small residual differences in selected race categories and healthcare utilization variables ( Table 1 ). Table 1 Before matching After matching IBS cohort (n=459,966) Control cohort (n=6,283,812) SMD IBS cohort (n=459,966) Control cohort (n=459,966) SMD Age at index Mean±SD 44.7±18.9 43.2±18.3 0.08 44.7±18.9 44.7±18.9 0.00 Sex Male 127727 (27.8) 2764418 (44.0) 0.34 127727 (27.8) 126855 (27.6) 0.00 Female 331852 (72.1) 3496674 (55.6) 0.35 331852 (72.1) 331853 (72.1) 0.00 Unknown Gender 387 (0.1) 22720 (0.4) 0.06 387 (0.1) 1258 (0.3) 0.04 Race, n (%) White 293269 (63.8) 3795904 (60.4) 0.07 293269 (63.8) 293309 (63.8) 0.00 Black or African American 29944 (6.5) 850969 (13.5) 0.24 29944 (6.5) 51385 (11.2) 0.16 Asian 19805 (4.3) 271824 (4.3) 0.00 19805 (4.3) 18313 (4.0) 0.02 Native Hawaiian or other Pacific Islander 626 (0.1) 16947 (0.3) 0.03 626 (0.1) 1108 (0.2) 0.02 American Indian or Alaska Native 1272 (0.3) 21365 (0.3) 0.01 1272 (0.3) 1452 (0.3) 0.01 Unknown Race 93845 (20.4) 976657 (15.5) 0.13 93845 (20.4) 70585 (15.3) 0.13 Other Race 21205 (4.6) 350146 (5.6) 0.04 21205 (4.6) 23814 (5.2) 0.03 Medical Utilization Status Ambulatory visit 366822 (79.8) 5107288 (81.3) 0.04 366822 (79.8) 375750 (81.7) 0.05 Emergency visit 119780 (26.0) 1531045 (24.4) 0.04 119780 (26.0) 111821 (24.3) 0.04 Inpatient encounter 89851 (19.5) 960921 (15.3) 0.11 89851 (19.5) 74061 (16.1) 0.09 Lifestyle Mental and behavioral disorders due to psychoactive substance use 36447 (7.9) 475752 (7.6) 0.01 36447 (7.9) 36436 (7.9) 0.00 Socioeconomic status Persons with potential health hazards related to socioeconomic and psychosocial circumstances 7361 (1.6) 112329 (1.8) 0.01 7361 (1.6) 9838 (2.1) 0.04 Family history Family history of arthritis and other diseases of the musculoskeletal system and connective tissue 1252 (0.3) 10875 (0.2) 0.02 1252 (0.3) 1030 (0.2) 0.01 BMI, n (%) ≧ 25 (kg/m2) 142526 (31.0) 2133398 (34.0) 0.06 142526 (31.0) 142533 (31.0) 0.00 C reactive protein, n (%) ≧ 5 (mg/L) 20414 (4.4) 143474 (2.3) 0.12 20414 (4.4) 11082 (2.4) 0.11 Comorbidities Essential hypertension 76862 (16.7) 1095075 (17.4) 0.02 76862 (16.7) 76873 (16.7) 0.00 Hyperlipidemia 44435 (9.7) 645883 (10.3) 0.02 44435 (9.7) 44417 (9.7) 0.00 Diabetes me
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