Review

Regulation of the Autoimmune and Allergic Responses by Short-chain Fatty Acids

Masato HIROTA, Chiaki YARIMIZU, Takahiro YAMADA, Daisuke TAKAHASHI, Koji HASE*

Graduate School of Pharmaceutical Science, Keio University

In recent years, there has been a marked increase in the incidence of autoimmune and allergic disorders. Many of them have been associated with intestinal dysbiosis, which is characterized by gut microbial imbalance or maladaptation. The human intestine is colonized by an estimated 100 trillion bacteria. Gut microbiota uses host-independent metabolic pathways to generate short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate through fermentation of dietary fiber. The gut microbiota associated with autoimmune and allergic disorders decreases SCFA-producing bacteria. SCFAs have shown beneficial effects in various experimental models of autoimmune and allergic disorders. For instance, butyrate promotes expansion of regulatory T cells in the colon to prevent excessive activation of effector T cells. In addition, SCFAs also enhance production of immunoglobulin A and play a protective role against intestinal infection through the activation of GPR41/Gpr43 and inhibition of histone deacetylase. In this review, we will focus on the pathological features of the dysbiosis associated with several autoimmune and allergic disorders. Furthermore, we will discuss the current mechanistic insights on the regulation of autoimmunity and allergies.
Key word: gut microbiota, dysbiosis, short-chain fatty acid, autoimmunity, allergy.

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