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We have demonstrated that AP disrupts the balance of the gut microbiota that aggravates disease progression; however, the role of gut microbiota in the development of SIRS\/CARS remains poorly understood. Here, we observed a lower abundance of\n                    <jats:italic>Bacteroides thetaiotaomicron<\/jats:italic>\n                    (\n                    <jats:italic>B. thetaiotaomicron<\/jats:italic>\n                    ) that increased the infiltration of PF4\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in AP patient and mouse models, which, in turn, promoted the recruitment of Th2 cells and neutrophils and exacerbated SIRS\/CARS. Supplementation with\n                    <jats:italic>B. thetaiotaomicron<\/jats:italic>\n                    increased the expression of the enzyme N\u2010methyltransferase (NMMT) and enhanced the production of 1\u2010methylnicotinamide (1MNA) in the gut epithelial cells, which inhibited PF4\n                    <jats:sup>+<\/jats:sup>\n                    macrophages dependent SIRS\/CARS by targeting ELF4, a transcript factor of PF4. Our findings provide novel interventions for AP patients with SIRS\/CARS through modulating gut microbiota.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511193","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:40:34Z","timestamp":1779806434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota Regulates Systemic Inflammatory Response and Compensatory Anti\u2010Inflammatory Response Syndromes by Targeting PF4\n                    <sup>+<\/sup>\n                    Macrophages in Acute Pancreatitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Liwei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Minimally Invasive Biliary Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education  Harbin 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