The effect of short-chain fatty acids on human monocyte-derived dendritic cells

Sci Rep. 2015 Nov 6;5:16148. doi: 10.1038/srep16148.

Abstract

The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrates / metabolism
  • Cells, Cultured
  • Chemokines, CXC / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Fatty Acids, Volatile / metabolism*
  • Gastrointestinal Microbiome / physiology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Inflammation / metabolism
  • Interleukin-12 Subunit p40 / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Propionates / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics

Substances

  • Butyrates
  • Chemokines, CXC
  • Fatty Acids, Volatile
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • Lipopolysaccharides
  • Propionates