{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gao H"],"funding":["BLRD VA","NIDDK NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","NINDS NIH HHS","U.S. Department of Veterans Affairs","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["565"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8799656"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["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."],"journal":["Nature communications"],"pubmed_title":["Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice."],"pmcid":["PMC8799656"],"funding_grant_id":["R01 DK125560","P30 NS047101","R01CA179977","R01 CA179977","P30 DK063491","R00DK115998","R01DK125560","I01 BX003934","R00 DK115998"],"pubmed_authors":["Tang K","Mahata S","Ly C","Luo Z","Sears DD","Ying W","Gao H","Ji Y","Jin Z"],"additional_accession":[]},"is_claimable":false,"name":"Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2025-04-04T08:41:22.765Z","creation":"2025-04-04T08:41:22.765Z"},"accession":"S-EPMC8799656","cross_references":{"pubmed":["35091566"],"doi":["10.1038/s41467-022-28239-2"]}}