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

2015; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/srep16148

2045-2322

Claudia Nastasi, Marco Candela, Charlotte M. Bonefeld, Carsten Geisler, Morten Hansen, Thorbjørn Krejsgaard, Elena Biagi, Mads Hald Andersen, Patrizia Brigidi, Niels Ødum, Thomas Litman, Anders Woetmann,

Helicobacter pylori-related gastroenterology studies

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.