The Effect of Short-chain Fatty Acids on Human Monocyte-derived Dendritic Cells

Overview

Journal Sci Rep

Specialty Science

Date 2015 Nov 7

PMID 26541096

Citations 186

Authors

Claudia Nastasi

Marco Candela

Charlotte Menne Bonefeld

Carsten Geisler

Morten Hansen

Thorbjorn Krejsgaard

Elena Biagi

Mads Hald Andersen

Patrizia Brigidi

Niels Odum

Thomas Litman

Anders Woetmann

Affiliations

Soon will be listed here.

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.

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