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SCFAs are produced by bacterial fermentation of fiber, mediating immune homeostasis through G\u2010protein\u2010coupled receptors (GPCRs). GPR109a, a receptor for niacin and butyrate, expressed by immune cells and non\u2010immune cells, is a key factor regulating immune responses. However, the role and underlying mechanisms of GPR109a in type 1 diabetes (T1D) remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Experimental T1D was induced by streptozotocin in GPR109a\u2010deficient (<jats:italic>Gpr109a<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) and wild type mice. The study found that <jats:italic>Gpr109a<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice were more susceptible to T1D with dysregulated immune responses, along with increased M1 macrophage polarization (from 10.55% to 21.48%). Further, an adoptive transfer experiment demonstrated that GPR109a\u2010deficient macrophages promoted the homing of intestine\u2010derived type 1 cytotoxic T\u00a0cells to pancreas (from 18.91% to 24.24%), thus disturbing the pancreatic immune homeostasis in non\u2010obese diabetic mice. Mechanistically, GPR109a deficiency promoted M1 macrophage polarization associated with the activation of suppressor of cytokine signaling 3\u2010signal transducer and activator of transcription 1 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D. Activation of GPR109a on macrophage by dietary components may provide a new strategy for preventing or treating T1D.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202200300","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T08:49:47Z","timestamp":1665218987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["GPR109a Regulates Phenotypic and Functional Alterations in Macrophages and the Progression of Type 1 Diabetes"],"prefix":"10.1002","volume":"66","author":[{"given":"Zhaodi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Food Science and Technology Department of Food Science and Engineering Jiangnan University  Wuxi 214122 China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi 214122 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