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

• Published in: Scientific reports Vol. 5; no. 1; p. 16148
• Main Authors: Nastasi, Claudia, Candela, Marco, Bonefeld, Charlotte Menné, Geisler, Carsten, Hansen, Morten, Krejsgaard, Thorbjørn, Biagi, Elena, Andersen, Mads Hald, Brigidi, Patrizia, Ødum, Niels, Litman, Thomas, Woetmann, Anders
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.11.2015; Nature Publishing Group
• Subjects: 13; 13/106; 13/31; 38; 38/61; 38/77; 38/90; 631/250; 631/80; 82; 82/80; Acetic acid; Butyrates - metabolism; CCL3 protein; CCL4 protein; Cells, Cultured; Chemokines; Chemokines, CXC - metabolism; CXCL10 protein; CXCL11 protein; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Fatty acids; Fatty Acids, Volatile - metabolism; Fermentation; Gastrointestinal Microbiome - physiology; Gene expression; Gene Expression - drug effects; Gene Expression - genetics; Humanities and Social Sciences; Humans; Inflammation; Inflammation - metabolism; Interleukin 12; Interleukin 6; Interleukin-12 Subunit p40 - metabolism; Interleukin-6 - metabolism; Intestinal microflora; Leukocytes - drug effects; Leukocytes - metabolism; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Metabolites; Monocytes; Monocytes - drug effects; Monocytes - metabolism; multidisciplinary; Propionates - metabolism; Propionic acid; Science; Transcription; Transcription, Genetic - drug effects; Transcription, Genetic - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep16148

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.