{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:46:57Z","timestamp":1793332017245,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A high prevalence of disorders of gut\u2010brain interaction (DGBI) exist in patients with hypermobile Ehlers\u2010Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD). However, it is unknown if clusters of hEDS\/HSD patients exist which overlap with different DGBIs and whether this overlap influences presence of comorbidities and quality of life. We aimed to study these knowledge gaps.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospectively collected hEDS\/HSD cohort of 1044 individuals were studied. We undertook Uniform Manifold Approximation and Projection\u2010enabled (UMAP) dimension reduction to create a representation of nonlinear interactions between hEDS\/HSD and DGBIs, from which individuals were stratified into clusters. Somatization, Postural Tachycardia Syndrome (PoTS), autonomic symptoms, psychological factors and quality of life were statistically compared between clusters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The mean age of patients was 40\u2009\u00b1\u200913.2\u2009years; 87.8% were female. Patients segregated into three clusters: Cluster 0 (<jats:italic>n<\/jats:italic>\u2009=\u2009466): hEDS\/HSD+ functional foregut disorders (FFD)\u2009+\u2009irritable bowel syndrome (IBS); Cluster 1 (<jats:italic>n<\/jats:italic>\u2009=\u2009180): hEDS\/HSD+ IBS and Cluster 2 (<jats:italic>n<\/jats:italic>\u2009=\u2009337): hEDS\/HSD alone. In cluster 0, we demonstrated increased somatization (<jats:italic>p<\/jats:italic>\u2009&lt;0.0001), anxiety (<jats:italic>p<\/jats:italic>\u2009&lt;0.0001), depression (<jats:italic>p<\/jats:italic>\u2009&lt;0.0001), PoTS prevalence (<jats:italic>p<\/jats:italic>\u2009=\u20090.003), autonomic symptoms (<jats:italic>p<\/jats:italic>\u2009&lt;0.0001) and reduced quality of life (<jats:italic>p<\/jats:italic>\u2009&lt;0.0001) compared to cluster 2. Cluster 0 had greater comorbidity burden than cluster 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Within hEDS\/HSD, subgroups exist with a high prevalence of FFD and IBS. These subgroups have a higher prevalence of psychological disorders, dysautonomia and poorer quality of life compared with hEDS\/HSD alone. Further research should focus on healthcare utilization, management and prognosis in hEDS\/HSD and DGBI overlap.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14957","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T05:24:33Z","timestamp":1731648273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A machine learning approach to stratify patients with hypermobile Ehlers\u2010Danlos syndrome\/hypermobility spectrum disorders according to disorders of gut brain interaction, comorbidities and quality of life"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-9798","authenticated-orcid":false,"given":"Anisa","family":"Choudhary","sequence":"first","affiliation":[{"name":"Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Fikree","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-7203","authenticated-orcid":false,"given":"James K.","family":"Ruffle","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"},{"name":"High Dimensional Neurology Group, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olafur S.","family":"Palsson","sequence":"additional","affiliation":[{"name":"Centre for Functional GI and Motility Disorders University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-2302","authenticated-orcid":false,"given":"Imran","family":"Aziz","sequence":"additional","affiliation":[{"name":"Academic Department of Gastroenterology Sheffield Teaching Hospitals and University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qasim","family":"Aziz","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31538"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.01.014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.02.034"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12665"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080321"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.421"},{"key":"e_1_2_9_9_1","volume-title":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","author":"Malfait F","year":"2017"},{"issue":"77","key":"e_1_2_9_10_1","first-page":"31","article-title":"Ehlers\u2010Danlos National Foundation (USA) and Ehlers\u2010Danlos Support Group (UK)","volume":"1998","author":"Beighton P","year":"1997","journal-title":"Am J Med Genet"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04402.x"},{"key":"e_1_2_9_12_1","first-page":"5","article-title":"How to score and interpret single\u2010item health status measures: a manual for users of the SF\u20108 health survey","volume":"15","author":"Ware JE","year":"2001","journal-title":"Lincoln, RI: Qual Metric Inc"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.166.10.1092"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1497.2001.016009606.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199303000-00006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.128.3.280"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.10.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0268-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","unstructured":"McinnesL HealyJ MelvilleJ.Umap: Uniform manifold approximation and projection for dimension reduction. arXiv preprint arXiv:1802.03426 2018.","DOI":"10.32614\/CRAN.package.uwot"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3268"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4854701"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13975"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13353"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33231"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000220"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5343-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12535"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2012.06.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000013115"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.856"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e32834f6ec9"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102227"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i20.6024"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.12.014"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2009.06.012"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14165"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013246900041"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000281999.56102.b5"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13810"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i22.6982"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13020293"},{"key":"e_1_2_9_43_1","first-page":"19","article-title":"Comparison of pyridostigmine and bisacodyl in the treatment of refractory chronic constipation","volume":"7","author":"Soufi\u2010Afshar I","year":"2016","journal-title":"Caspian J Intern Med"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.25"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.06.018"},{"key":"e_1_2_9_46_1","first-page":"93","article-title":"Postural tachycardia syndrome and Neurally mediated syncope","volume":"26","author":"Cutsforth\u2010Gregory JK","year":"2020","journal-title":"Continuum (Minneap Minn)"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.2011.03047.x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2006.12.003"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13756"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pecinn.2022.100050"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.14957","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:17:59Z","timestamp":1739783879000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.14957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,14]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/nmo.14957"],"URL":"https:\/\/doi.org\/10.1111\/nmo.14957","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,14]]},"assertion":[{"value":"2024-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14957"}}