title: The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models.
abstract: Autoimmune diseases are influenced by both genetic and environmental factors. The gut environment has attracted much attention as an essential component that modulates immune responses, and therefore immune-mediated disorders, such as autoimmune diseases. Growing evidence suggests that microbiota and their metabolites are critical factors for immune modulation. Recently, we reported that the microbiome in patients with multiple sclerosis, an autoimmune disease targeting the myelin sheath of the central nervous system, is characterized by a reduction of bacteria belonging to Clostridia clusters IV and XIVa, which are potent producers of short-chain fatty acids (SCFAs) by fermentation of indigestible carbohydrates. In the present study, we investigated the role of SCFAs in the regulation of inflammation. We demonstrated that oral administration of SCFAs ameliorated the disease severity of systemic autoimmune inflammatory conditions mediated by lymphocytes such as experimental autoimmune encephalitis and collagen-induced arthritis. Amelioration of disease was associated with a reduction of Th1 cells and an increase in regulatory T cells. In contrast, SCFAs contributed to the exaggeration of K/BxN serum transfer arthritis, representing the effector phase of inflammation in rheumatoid arthritis. An increased understanding of the effect of microbiota metabolites will lead to the effective treatment and prevention of systemic inflammatory disorders.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Noto
authors.affiliation: Laboratory of Proteomics and Biomolecular Science Research Support Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kaga
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Chiba
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005232:Fatty Acids, Volatile / Q000008:administration & dosage*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D005232:Fatty Acids, Volatile