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The impact of the gut microbiome on extra-intestinal autoimmune diseases

Abstract

The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. Faecal microbiota transplantation or inoculation with specific microbes in animal models of ADs support the hypothesis that alterations of gut microbiota influence autoimmune responses and disease outcome. Here, we describe the compositional and functional changes in the gut microbiota in patients with extra-intestinal AD and discuss how the gut microbiota affects immunity. Moreover, we examine how the gut microbiota might be modulated in patients with ADs as a potential preventive or therapeutic approach.

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Fig. 1: Intestinal commensal bacteria can modulate autoreactive T cells and inflammation in the CNS.
Fig. 2: Regulatory function of helminths and intestinal commensal bacteria in autoimmune-mediated diabetes.
Fig. 3: Proposed study design to develop microbiome modulation strategies.

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Acknowledgements

Work in the authors’ laboratory was supported by the following grants: the research grant of Astellas Foundation for Research on Metabolic Disorders and JSPS KAKENHI Grant Number 19K05907 to E.M.; JSPS KAKENHI Grant Number 19K16682, Naito foundation, Yakult Bio-Science Foundation, Shiseido Female Researcher Science Grant, The Nakajima Foundation, Uehara Memorial Foundation, and Mochida Memorial Foundation for Medical and Pharmaceutical Research to C.S.; Luxembourg National Research Fund (FNR) CORE grant (C18/BM/12585940) and FNR INTER Mobility grant (16/11455695) to M.S.D.; and AMED-CREST (19gm0710009h0006), JSPS KAKENHI Grant Number 19H01030, and the Food Science Institute Foundation to H.O.

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Miyauchi, E., Shimokawa, C., Steimle, A. et al. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat Rev Immunol 23, 9–23 (2023). https://doi.org/10.1038/s41577-022-00727-y

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