{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:30:45Z","timestamp":1792539045856,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2004495"],"award-info":[{"award-number":["APP2004495"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with Ehlers\u2013Danlos syndrome (EDS)\/hypermobility spectrum disorders (HSD) report higher rates of chronic gastrointestinal (GI) symptoms, disorders of gut\u2013brain interaction (DGBI), and extraintestinal comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta\u2010analysis to assess the prevalence of chronic GI symptoms and comorbid conditions in hEDS\/HSD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Electronic databases were searched until December 2025 for studies reporting on chronic GI symptoms in hEDS\/HSD patients. Pooled prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated using the random effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final dataset of 19 studies included 17,455 hEDS\/HSD patients and 1,677,465 controls. The odds of chronic GI symptoms were higher in patients with hEDS\/HSD compared to controls (OR 4.29, 95% CI 3.1\u20136.0). 65.3% (95% CI 51.4\u201377.0) of hEDS\/HSD patients reported at least one chronic GI symptom, with heartburn being the most common (34.7%, 95% CI 28.3\u201341.7). The prevalence of DGBI in hEDS\/HSD patients was 44.2% (95% CI 23.9\u201366.6), with functional dysphagia the most common DGBI at 34.2% (95% CI 25.7\u201343.8). Gastroesophageal reflux disease was reported in 41.3% (95% CI 27.2\u201357.0). In hEDS\/HSD patients, the most common extraintestinal comorbidity was chronic fatigue (49%, 95% CI 34.6\u201363.6), followed by migraine (38.2%, 95% CI 19.9\u201360.5), orthostatic intolerance (OI) (35.9%, 95% CI 26.6\u201346.4), fibromyalgia (27.9%, 95% CI 16.0\u201344.0) and postural orthostatic tachycardia syndrome (POTS) (21.9%, 95% CI 5.2\u201359.1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, &gt;\u200960% of hEDS\/HSD patients report chronic GI symptoms. DGBI, co\u2010morbidities, including POTS, were highly prevalent in hEDS\/HSD patients. However, the quality of the evidence is low due to significant clinical heterogeneity observed in the analyses. While the associations may suggest a causal relationship, the results should be interpreted with caution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70856","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T14:12:12Z","timestamp":1783865532000},"page":"574-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Meta\u2010Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers\u2013Danlos Syndrome and Hypermobility Spectrum Disorders"],"prefix":"10.1111","volume":"64","author":[{"given":"Dmitrii","family":"Kulin","sequence":"first","affiliation":[{"name":"Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"},{"name":"Translational Research Institute  Brisbane Queensland Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Holtmann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"},{"name":"Translational Research Institute  Brisbane Queensland Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fairlie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"},{"name":"Translational Research Institute  Brisbane Queensland Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-4290","authenticated-orcid":false,"given":"Kyle","family":"Staller","sequence":"additional","affiliation":[{"name":"Centre for Neurointestinal Health, Division of Gastroenterology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0936-4807","authenticated-orcid":false,"given":"Samuel","family":"Nurko","sequence":"additional","affiliation":[{"name":"Centre for Motility and Functional Gastrointestinal Disorders Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4779-8593","authenticated-orcid":false,"given":"Laurie","family":"Keefer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Icahn School of Medicine at Mount Sinai  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Drossman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of N.C. and Drossman Gastroenterology  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-4938","authenticated-orcid":false,"given":"Michael P.","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences Macquarie University  North Ryde Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qasim","family":"Aziz","sequence":"additional","affiliation":[{"name":"Wingate Institute of Neurogastroenterology, Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0710-1691","authenticated-orcid":false,"given":"Ayesha","family":"Shah","sequence":"additional","affiliation":[{"name":"Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"},{"name":"Translational Research Institute  Brisbane Queensland Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15927"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31538"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61055"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-022-09280-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000541"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2478\/rir-2023-0010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-031365"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.02.034"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13975"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14957"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro\u20102025\u2010103250"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664-020-01107-x"},{"key":"e_1_2_10_17_1","first-page":"S446","article-title":"Presence of Functional Gastrointestinal Disorders (FGIDs) in Pediatric Patients With Ehlers\u2010Danlos Syndrome or Joint Hypermobility Syndrome and Postural Orthostatic Tachycardia Syndrome. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Annual Meeting, NASPGHAN 2021","volume":"73","author":"Solomon V.","year":"2021","journal-title":"Virtual: Journal of Pediatric Gastroenterology and Nutrition"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/XEB.0000000000000054"},{"key":"e_1_2_10_19_1","unstructured":"G. A.Wells B.Shea D.O'Connell et\u00a0al. \u201cThe Newcastle\u2010Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta\u2010Analyses \u201d(2000)."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01381-z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33231"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080321"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12665"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa926"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh279"},{"key":"e_1_2_10_26_1","article-title":"Prevalence and Predictors of Gastrointestinal Dysmotility in Patients With Hypermobile Ehlers\u2010Danlos Syndrome: A Tertiary Care Center Experience","volume":"12","author":"Alomari M.","year":"2020","journal-title":"Cureus"},{"key":"e_1_2_10_27_1","first-page":"998","article-title":"Symptom and Joint Mobility Progression in the Joint Hypermobility Syndrome (Ehlers\u2010Danlos Syndrome, Hypermobility Type)","volume":"29","author":"Castori M.","year":"2011","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4854701"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06265-8"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12942"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14077"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-019-04293-w"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001173"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-023-08201-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16341"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2020.1761890"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31546"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2022-102088"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl230396"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"e_1_2_10_41_1","first-page":"479","article-title":"The Suggested Relationships Between Common GI Symptoms and Joint Hypermobility, POTS, and MCAS","volume":"20","author":"Quigley E. M. M.","year":"2024","journal-title":"Gastroenterology and Hepatology"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2025.02.015"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-019-08755-8"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2018.04.004"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2021.42.210022"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003315"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.803614"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31431"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.70856","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:22:48Z","timestamp":1791904968000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.70856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,12]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/apt.70856"],"URL":"https:\/\/doi.org\/10.1111\/apt.70856","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,12]]},"assertion":[{"value":"2026-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}