title: Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo.
abstract: Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ciarlo
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Tytti
authors.initials: T
authors.lastname: Heinonen
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Jacobus
authors.initials: J
authors.lastname: Herderschee
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Craig
authors.initials: C
authors.lastname: Fenwick
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Mombelli
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Le Roy
authors.affiliation: Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000276:immunology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005260:Female; D005658:Fungi / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D011422:Propionates / Q000494:pharmacology*
chemical_list: D005232:Fatty Acids, Volatile; D011422:Propionates