title: The effect of short-chain fatty acids on human monocyte-derived dendritic cells.
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.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nastasi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Candela
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Charlotte Menné
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Biagi
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Brigidi
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Ødum
authors.affiliation: Translational Research, LEO Pharma, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
mesh_terms: D002087:Butyrates / Q000378:metabolism; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D002087:Butyrates; D019743:Chemokines, CXC; D005232:Fatty Acids, Volatile; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011422:Propionates