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

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

Author information

1
Department of Immunology and Microbiology, University of Copenhagen, Denmark.
2
Department of Pharmacy and Biotechnology, University of Bologna, Italy.
3
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
4
Translational Research, LEO Pharma, Denmark.

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.

PMID:
26541096
PMCID:
PMC4635422
DOI:
10.1038/srep16148
[Indexed for MEDLINE]
Free PMC Article

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