The Role of Gut Microbiome-Derived Short-Chain Fatty Acid Butyrate in Hepatobiliary Diseases

Am J Pathol. 2023 Oct;193(10):1455-1467. doi: 10.1016/j.ajpath.2023.06.007. Epub 2023 Jul 6.

Abstract

The short-chain fatty acid butyrate, produced from fermentable carbohydrates by gut microbiota in the colon, has multiple beneficial effects on human health. At the intestinal level, butyrate regulates metabolism, helps in the transepithelial transport of fluids, inhibits inflammation, and induces the epithelial defense barrier. The liver receives a large amount of short-chain fatty acids via the blood flowing from the gut via the portal vein. Butyrate helps prevent nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, inflammation, cancer, and liver injuries. It ameliorates metabolic diseases, including insulin resistance and obesity, and plays a direct role in preventing fatty liver diseases. Butyrate has different mechanisms of action, including strong regulatory effects on the expression of many genes by inhibiting the histone deacetylases and modulating cellular metabolism. The present review highlights the wide range of beneficial therapeutic and unfavorable adverse effects of butyrate, with a high potential for clinically important uses in several liver diseases.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrates / metabolism
  • Fatty Acids, Volatile / pharmacology
  • Fatty Acids, Volatile / therapeutic use
  • Gastrointestinal Microbiome*
  • Humans
  • Inflammation / drug therapy
  • Non-alcoholic Fatty Liver Disease* / drug therapy

Substances

  • Butyrates
  • Fatty Acids, Volatile