Modulation of autoimmune arthritis by environmental 'hygiene' and commensal microbiota

Abstract

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.

Keywords: Arthritis; Aryl hydrocarbon receptor; Autoimmunity; Hygiene hypothesis; Indoles; Metabolites; Microbiome; Microbiota; Natural products; Prebiotics; Probiotics; Rheumatoid arthritis; Short-chain fatty acids; Th17/Treg balance; Tryptophan.

Fig. 1.

The ‘Hygiene hypothesis’ proposes an imbalance in the host immune response (e.g., Th1 versus Th2; Th17/Treg) to various environmental agents and pathogens such that the host is rendered more prone to allergies and autoimmunity, while retaining the ability to fight effectively against certain infectious pathogens.

Fig. 2.

The impact of dietary and other exogenous compounds on the maintenance of health, regulation of the host immune system through specific metabolites, and homeostasis of the host microbiome. Perturbation of microbial composition and the metabolites generated either by them and/or from their dietary substrates may result in chronic inflammation locally and at peripheral sites (e.g., the joints).