{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:41:13Z","timestamp":1789422073749,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients with diabetes exhibit increased susceptibility to myocardial ischemia\/reperfusion (IR) injury. Emerging evidence highlights gut microbiota-derived microbial metabolites as critical modulators of the gut\u2013heart axis. This study examined the pathological role of succinate, a crucial metabolite derived from the microbiota, in the progression of diabetic myocardial IR injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The gut microbiota composition and succinate levels in diabetic mice were analyzed. Changes in succinate levels were subsequently assessed following the depletion of the gut microbiota induced by antibiotics. Diabetic mice with genetic ablation of Sucnr1 were administered exogenous succinate supplementation prior to IR induction. In vitro, conditioned medium transfer systems were utilized to coculture macrophages with cardiomyocytes subjected to hypoxia\/reoxygenation injury, and the extent of cardiomyocyte damage was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cardiac succinate accumulation during diabetes progression is linked to gut microbial dysbiosis, which is characterized by an imbalance between succinate-producing and succinate-consuming bacteria. Antibiotic-mediated depletion of the gut microbiota reversed this succinate accumulation, demonstrating that microbial communities constitute a major source of cardiac succinate. Furthermore, succinate drove the polarization of cardiac macrophages and exacerbated diabetes-associated myocardial IR injury. Conversely, genetic knockdown of Sucnr1 in both in vitro and in vivo models ameliorated the detrimental effects of succinate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Cardiac succinate accumulation occurs during diabetes progression and is associated with specific gut microbial dysbiosis, which is characterized by a disrupted equilibrium between succinate-producing and succinate-consuming bacteria. This pathological accumulation of succinate exacerbates diabetes-associated myocardial IR injury by driving macrophage polarization through activation of the SUCNR1 signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1749185","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:29:22Z","timestamp":1781065762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Gut microbiota-induced elevation of succinate exacerbates diabetic myocardial ischemia\/reperfusion injury by promoting macrophage polarization"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, 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