Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, San Diego, CA, United States.
Division of Biological Sciences, University of California San Diego, San Diego, CA, United States.
Front Immunol. 2023 Jul 13;14:1216344. doi: 10.3389/fimmu.2023.1216344. eCollection 2023.
Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into cardiomyocytes in ageing mice, causing cardiac microbial DNA enrichment. Vsig4 macrophages efficiently block the spread of gut mEVs whereas Vsig4 cell population was greatly decreased in ageing mice. Gut mEV treatment resulted in cardiac inflammation and a reduction in cardiac contractility in young Vsig4 mice. Microbial DNA depletion attenuated the pathogenic effects of gut mEVs. cGAS/STING signaling is critical for the effects of microbial DNA. Restoring Vsig4 macrophage population in ageing WT mice reduced cardiac microbial DNA abundance and inflammation and improved heart contractility.
新出现的证据表明，微生物组在介导宿主心脏功能衰老中起着关键作用，然而，在衰老过程中微生物组与心脏细胞之间的通讯机制尚未完全阐明。细菌 DNA 在衰老的人类和小鼠的心肌细胞中富集。抗生素治疗显著降低了衰老小鼠的细菌 DNA 丰度。含有细胞外囊泡 (mEV) 的肠道微生物 DNA 很容易渗漏到血液中，并渗透到衰老小鼠的心肌细胞中，导致心脏微生物 DNA 富集。Vsig4 巨噬细胞能有效阻止肠道 mEV 的传播，而衰老小鼠中 Vsig4 细胞群大大减少。肠道 mEV 处理导致年轻的 Vsig4 小鼠心脏炎症和收缩力下降。微生物 DNA 耗竭可减轻肠道 mEV 的致病作用。cGAS/STING 信号通路对微生物 DNA 的作用至关重要。在衰老的 WT 小鼠中恢复 Vsig4 巨噬细胞群可减少心脏微生物 DNA 丰度和炎症，并改善心脏收缩力。
