Gut Microbially Produced Butyric Acid Impedes CAVD Pathogenesis by Mediates Competitive Modification of Lactylation and Butyrylation

Easy and difficult calcification ApoE-/- mice were divided via neural network and cluster analyses, and the combination of fecal transplantation and dirty cage sharing demonstrating that the microbiota from difficult calcification mice ameliorated CAVD. An unbiased microbiome analyses identified the difficult calcification mice harbored a distinct gut microbiome compare to calcification prone mice. The reduced abundance of Faecalibacterium prausnitzii (F. prausnitzii) was associated with higher calcification degree in a striking statistically significant fashion. Association analysis provided direct evidence for the important role of F. prausnitzii-derived butyric acid (BA) in the anti-calcification function. Clinical relevance in humans was supported by a comparative correlation analysis of blood butyric acid content and clinicopathology in healthy and CAVD patients. Treatment with BA effective hindered the osteogenic differentiation in human aortic valve interstitial cells (hVICs) and retarded CAVD progression in mice.