The microbiome and autoimmunity: a paradigm from the gut–liver axis

Bo Li, Carlo Selmi, Ruqi Tang, M. Eric Gershwin, Xiong Ma

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut–liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.

Original languageEnglish (US)
Pages (from-to)595-609
Number of pages15
JournalCellular and Molecular Immunology
Volume15
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Microbiota
Autoimmunity
Dysbiosis
Autoimmune Diseases
Bystander Effect
Germ-Free Life
Molecular Mimicry
Th17 Cells
Immune Tolerance
Rheumatic Fever
Autoantigens
Adaptive Immunity
Helper-Inducer T-Lymphocytes
Streptococcus
Type 1 Diabetes Mellitus
Innate Immunity
Multiple Sclerosis
Liver Diseases
Epitopes
Rheumatoid Arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

The microbiome and autoimmunity : a paradigm from the gut–liver axis. / Li, Bo; Selmi, Carlo; Tang, Ruqi; Gershwin, M. Eric; Ma, Xiong.

In: Cellular and Molecular Immunology, Vol. 15, No. 6, 01.06.2018, p. 595-609.

Research output: Contribution to journalReview article

Li, Bo ; Selmi, Carlo ; Tang, Ruqi ; Gershwin, M. Eric ; Ma, Xiong. / The microbiome and autoimmunity : a paradigm from the gut–liver axis. In: Cellular and Molecular Immunology. 2018 ; Vol. 15, No. 6. pp. 595-609.
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