Modulation of autoimmune arthritis by environmental ‘hygiene’ and commensal microbiota

• Published in: Cellular immunology Vol. 339; pp. 59 - 67
• Main Authors: Langan, David, Kim, Eugene Y., Moudgil, Kamal D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2019
• Subjects: Animals; Arthritis; Arthritis, Rheumatoid - immunology; Aryl hydrocarbon receptor; Autoimmune Diseases - immunology; Autoimmunity; Autoimmunity - immunology; Dysbiosis - immunology; Gastrointestinal Microbiome - immunology; Humans; Hygiene hypothesis; Indoles; Metabolites; Microbiome; Microbiota; Natural products; Prebiotics; Probiotics; Rheumatoid arthritis; Short-chain fatty acids; T-Lymphocyte Subsets - immunology; Th17/Treg balance; Tryptophan; Autoimmunity; T1D; SPF; TCDD; IBD; Arthritis; Bhsp65; Microbiota; Metabolites; CIA; Indoles; Th17; Trp-C; GF; AA; Short-chain fatty acids; Hsp; MS; Treg; EAE; Hygiene hypothesis; Tryptophan; AhR; LAB; SCFA; BCTD; RA; Prebiotics; Aryl hydrocarbon receptor; Probiotics; CV; Th17/Treg balance; Natural products; Rheumatoid arthritis; Microbiome
• ISSN: 0008-8749; 1090-2163; 1090-2163
• DOI: 10.1016/j.cellimm.2018.12.005

•Environment plays a significant role in the pathogenesis of autoimmune arthritis.•‘Hygiene hypothesis’ suggests inverse relationship between infection and autoimmunity.•Gut microbiota is critical for Th17/Treg balance and protection against autoimmunity.•Many functional attributes of microbiota are mediated via microbial metabolites.•Gut dysbiosis can be re-set in part via pre-/pro-biotics and fecal transplantation. Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis. It is hoped that advances in defining the interplay between gut microbiota, dietary products, and bioactive metabolites would help in the development of therapeutic regimen customized for the needs of individual patients in the near future.