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Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate\u2010producing probiotic (EcNP3) to achieve sustained restoration of propionate levels in the gut and increase its bioavailability. DSS\u2010induced experimental intestinal inflammation model was used to evaluate the effect of EcNP3 on improving the intestinal mucosal barrier and increasing the proportion of anti\u2010inflammatory macrophages. It was found that EcNP3 exhibited a restorative effect on the depletion of peritoneal anti\u2010inflammatory macrophages (F4\/80hiCD11bhi) and significantly improved the expression level of IL\u201010. Simultaneously, the expression of IL\u20101\u03b2, IL\u20106, and CXCL1 was downregulated while inhibiting apoptosis of tissue\u2010resident macrophages ex vivo. Further investigation revealed that EcNP3 regulates IL\u201010 expression through G protein\u2010coupled receptor 43 and histone deacetylase. Furthermore, EcNP3 significantly inhibited the protein expression of HDAC1 and promoted the histone acetylation level of cells. Finally, EcNP3 significantly improved DSS\u2010induced colitis in mice by increasing mucus production and reducing inflammatory infiltration. Our results suggest that the engineered live biotherapeutic product EcNP3 is a safe and potently efficacious treatment for IBD, which defines a novel strategy in IBD therapy through macrophage IL\u201010 signaling.<\/jats:p>","DOI":"10.1002\/btm2.10682","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T08:19:44Z","timestamp":1716797984000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Propionate\u2010producing engineered probiotics ameliorated murine ulcerative colitis by restoring anti\u2010inflammatory macrophage via the\n                    <scp>GPR43<\/scp>\n                    \/\n                    <scp>HDAC1<\/scp>\n                    \/\n                    <scp>IL<\/scp>\n                    \u201010 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