biostudies-literatureGao HBLRD VANIDDK NIH HHSU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSNINDS NIH HHSU.S. Department of Veterans AffairsU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases565https://www.ebi.ac.uk/biostudies/studies/S-EPMC8799656biostudies-literatureUnknown13(1)Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.Nature communicationsAccumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice.PMC8799656R01 DK125560P30 NS047101R01CA179977R01 CA179977P30 DK063491R00DK115998R01DK125560I01 BX003934R00 DK115998Tang KMahata SLy CLuo ZSears DDYing WGao HJi YJin ZfalseAccumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice.Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.2022-01-01T00:00:00Z2022 Jan2025-04-04T08:41:22.765Z2025-04-04T08:41:22.765ZS-EPMC87996563509156610.1038/s41467-022-28239-2