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Extended mesenteric excision can reduce surgical recurrence and improve long\u2010term outcomes, indicating that MAT plays an important role in the pathogenesis of CD. Bacterial translocation has been reported to occur in\u00a0the MAT\u00a0of patients\u00a0with\u00a0CD (CD\u2010MAT), but the mechanisms by which translocated bacteria lead to intestinal colitis remain unclear. Here it is shown that members of Enterobacteriaceae are highly enriched in CD\u2010MAT compared with non\u2010CD controls. Viable <jats:italic>Klebsiella variicola<\/jats:italic> in Enterobacteriaceae is isolated exclusively in CD\u2010MAT and can induce a pro\u2010inflammatory response in vitro and exacerbates colitis both in dextran sulfate sodium (DSS)\u2010induced colitis mice model and <jats:italic>IL\u201010<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> spontaneous colitis mice model. Mechanistically, active type VI secretion system (T6SS) is identified in the genome of <jats:italic>K. variicola<\/jats:italic>, which can impair the intestinal barrier by inhibiting the zonula\u00a0occludens\u00a0(ZO\u20101)\u00a0expression. Dysfunction of T6SS by CRISPR interference system alleviates the inhibitory effect of <jats:italic>K. variicola<\/jats:italic> on ZO\u20101 expression and attenuated colitis in mice. Overall, these findings demonstrate that a novel colitis\u2010promoting bacteria exist in the mesenteric adipose tissue of CD, opening a new therapeutic avenue for colitis management.<\/jats:p>","DOI":"10.1002\/advs.202205272","type":"journal-article","created":{"date-parts":[[2023,2,19]],"date-time":"2023-02-19T22:17:52Z","timestamp":1676845072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Mesenteric Adipose Tissue\u2010Derived <i>Klebsiella variicola<\/i> Disrupts Intestinal Barrier and Promotes Colitis by Type VI Secretion System"],"prefix":"10.1002","volume":"10","author":[{"given":"Junli","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 510655 P. R. 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