Role of short-chain fatty acids in host physiology

Abstract

Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.

Keywords: gut microbiota; host; interaction relationship; short‐chain fatty acids.

FIGURE 1

SCFAs produced by the intestinal flora inhibit HADC and activate GPCRs. Intestinal flora metabolizes dietary fiber to form short‐chain fatty acids, which can activate GPCRS (GCPR43/FFAR2) and further regulate intestinal secretion of antimicrobial peptide YY. Butyric acid, one of the short‐chain fatty acids is an inhibitor of HDAC, and can inhibit macrophages and reduce the production of TNF‐α, IL‐6, and IL‐12.

FIGURE 2

Mechanisms by which SCFAs are associated with different hosts conditions. SCFAs protect the intestinal mucosa barrier to promote intestinal health; SCFAs can inhibition colorectal cancer; SCFAs regulate energy metabolism to inhibit obesity; SCFAs can alleviate diabetes by being anti‐inflammatory and stabilizing the intestinal environment; SCFAs regulate intestinal hormone secretion and stabilize the gut‐brain axis; SCFAs regulate the gut‐brain axis by anti‐inflammatory and antiviral action; SCFAs regulate bone cell metabolism and bone mass to protect bone health thus offering promising avenues for future research.