Epigenetic connection between gut microbiota-derived short-chain fatty acids and chromatin histone modification in kidney diseases

Abstract

Gut microbiota-derived metabolites influence host physiology and pathology, where short-chain fatty acids (SCFAs) are the main class of gut microbiota-derived metabolites. [1] SCFAs are fatty acids containing 1 to 6 carbon atoms, including acetate, propionate, butyrate, and pentanoate, which provide 6% to 10% of the body's total daily energy and 60% to 70% of the colonic epithelial energy needed. [2] Anaerobic bacteria principally generate the SCFAs [1] in the intestine. Once produced, SCFAs are mainly absorbed in the colon (90%-95%), reach circulation, and play roles for distal organs and tissues. [2]

The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity

“…SCFAs were also shown to affect histone acetylation and methylation beyond the intestine, as they epigenetically regulate gene expression in the liver, kidney and fat tissue ( 208 , 261 ). Mice fed a Western diet showed decreased levels of SCFA resulting in altered histone modifications ultimately regulating hepatic metabolism via PPAR signaling, genes involved in insulin and cholesterol pathways, as well as genes related to adaptive immunity, lipid, retinol, and amino acid metabolism ( 208 ).…”

“…Moreover, butyrate was shown to decrease T helper cell (Th) 17 expression and increase Th1 via histone acetylation (258,259). On top of that, SCFA enhance interferon g (IFNg) expression in cytotoxic T lymphocytes (CTLs) via HDAC inhibition, crucial for mediating anti-tumor effects (260).…”