Gut microbiota-derived short-chain fatty acids and their role in human health and disease

Nat Rev Microbiol. 2025 Oct;23(10):635-651. doi: 10.1038/s41579-025-01183-w. Epub 2025 May 13.

Abstract

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.

Publication types

  • Review

MeSH terms

  • Animals
  • Dietary Fiber / metabolism
  • Fatty Acids, Volatile* / metabolism
  • Fermentation
  • Gastrointestinal Microbiome* / physiology
  • Gastrointestinal Tract* / microbiology
  • Humans

Substances

  • Fatty Acids, Volatile
  • Dietary Fiber