Microbial DNA Leaks from the Aging Intestines to Cause Harmful Inflammation in the Heart

Researchers here find that, in mice, microbial DNA from the aging gut readily leaks into circulation. The aging innate immune system falters in its ability to clear this DNA due to a declining population of macrophages capable of this task. As a consequence the microbial DNA provokes inflammatory dysfunction in the heart. This is an interesting advance in understanding the specifics of the broad relationship between the gut microbiome and degenerative aging, and offers pointers to ways in which the aging immune function might be improved.

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.

Link: https://doi.org/10.3389/fimmu.2023.1216344