{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:07:20Z","timestamp":1793578040886,"version":"4.5.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Institutional National Research Service Award","award":["T32-DK007130-45"],"award-info":[{"award-number":["T32-DK007130-45"]}]},{"DOI":"10.13039\/100007827","name":"American College of Gastroenterology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fistulising perianal involvement is a common presentation of Crohn\u2019s disease. Perianal Crohn\u2019s disease dramatically impairs patients\u2019 social and sexual life and its management remains a critical challenge in field of inflammatory bowel disease. No medical therapy is specifically designed for the treatment of perianal Crohn\u2019s disease, largely due to the poorly understood pathophysiology. Limited evidence from preclinical and clinical studies suggests that the initiation, progression, and maintenance of Crohn\u2019s disease-associated perianal fistulas involves complex interactions between host, microbial, and environmental factors. This review intends to discuss the possible roles of genetic predisposition, mucosal immunity, and gut microbiome in perianal Crohn\u2019s disease, and considers how epithelial-to-mesenchymal transition may contribute to the pathogenesis. It also summarises recent advances on the development of animal models and new therapies for perianal Crohn\u2019s disease. At the end, we discussed future directions in basic, translational, and clinical research that may dramatically improve our understanding of perianal Crohn\u2019s disease and open avenues for novel therapeutic strategies with a multidisciplinary approach. Overall, this review aims to identify current gaps in understanding of perianal fistulising Crohn\u2019s disease and to explore future research priorities for this debilitating condition.<\/jats:p>","DOI":"10.1093\/ecco-jcc\/jjad008","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T14:55:44Z","timestamp":1673967344000},"page":"1010-1022","source":"Crossref","is-referenced-by-count":38,"title":["Pathogenesis of Perianal Fistulising Crohn\u2019s Disease: Current Knowledge, Gaps in Understanding, and Future Research Directions"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-2164","authenticated-orcid":false,"given":"Siyan","family":"Cao","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Washington University School of Medicine , St Louis, MO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St Louis, MO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-9784","authenticated-orcid":false,"given":"Parakkal","family":"Deepak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Washington University School of Medicine , St Louis, MO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"2023061613185400100_CIT0001","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1053\/gast.2002.32362","article-title":"The natural history of fistulizing Crohn\u2019s disease in Olmsted County, 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