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In this study, we investigated the effects of DHA in a dextran sulfate sodium (DSS)-induced mouse model of colitis and examined whether these effects were mediated by the gut microbiota. DHA administration markedly alleviated DSS-induced colitis, as indicated by reduced body weight loss, disease activity, mortality, colon shortening, histological injury, intestinal barrier disruption, and colonic inflammatory responses. 16\u00a0S rRNA gene sequencing showed that DHA reshaped the gut microbial community and increased the abundance of beneficial taxa, including\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    . Antibiotic cocktail (ABX)-mediated microbiota depletion largely abolished the protective effects of DHA, whereas fecal microbiota transplantation (FMT) from DHA-treated donors transferred resistance to DSS-induced colitis to recipient mice. DHA also restored tight junction protein expression and increased the frequency of colonic regulatory T cells in a microbiota-dependent manner. These findings indicate that DHA alleviates experimental colitis by modulating the gut microbiota, restoring intestinal barrier integrity, and regulating mucosal immune homeostasis. DHA may therefore represent a promising dietary strategy for the prevention or adjunctive treatment of ulcerative colitis (UC).\n                  <\/jats:p>","DOI":"10.1007\/s10123-026-00859-4","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:27:03Z","timestamp":1783045623000},"page":"1451-1463","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Docosahexaenoic acid alleviates DSS-induced colitis by regulating the gut microbiota and restoring the gut barrier"],"prefix":"10.1007","volume":"29","author":[{"given":"Sumin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanneng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"859_CR1","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1007\/s00394-020-02413-y","volume":"60","author":"SM Ajabnoor","year":"2021","unstructured":"Ajabnoor SM, Thorpe G, Abdelhamid A, Hooper L (2021) Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials. 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