Journal Article

The Role of the Microbiota in Graves’ Disease and Graves’ Orbitopathy

Hou, Jueyu, Chen, Danian, Tang, Yunjing, Chen, Yongjiang

2021

Overview

Graves‘ disease (GD) is a clinical syndrome with an enlarged and overactive thyroid gland, an accelerated heart rate, Graves’ orbitopathy (GO), and pretibial myxedema (PTM). GO is the most common extrathyroidal complication of GD. GD/GO has a significant negative impact on the quality of life. GD is the most common systemic autoimmune disorder, mediated by autoantibodies to the thyroid-stimulating hormone receptor (TSHR). It is generally accepted that GD/GO results from complex interactions between genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens. However, the exact mechanism is still elusive. Systematic investigations into GD/GO animal models and clinical patients have provided important new insight into these disorders during the past 4 years. These studies suggested that gut microbiota may play an essential role in the pathogenesis of GD/GO. Antibiotic vancomycin can reduce disease severity, but fecal material transfer (FMT) from GD/GO patients exaggerates the disease in GD/GO mouse models. There are significant differences in microbiota composition between GD/GO patients and healthy controls. Lactobacillus , Prevotella , and Veillonella often increase in GD patients. The commonly used therapeutic agents for GD/GO can also affect the gut microbiota. Antigenic mimicry and the imbalance of T helper 17 cells (Th17)/regulatory T cells (Tregs) are the primary mechanisms proposed for dysbiosis in GD/GO. Interventions including antibiotics, probiotics, and diet modification that modulate the gut microbiota have been actively investigated in preclinical models and, to some extent, in clinical settings, such as probiotics ( Bifidobacterium longum ) and selenium supplements. Future studies will reveal molecular pathways linking gut and thyroid functions and how they impact orbital autoimmunity. Microbiota-targeting therapeutics will likely be an essential strategy in managing GD/GO in the coming years.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animal models / Animals / Antibiotics / Autoantibodies / Autoimmunity / Cellular and Infection Microbiology / Dysbacteriosis / Environmental factors / Females / Fibroblasts / Gastrointestinal Microbiome / Graves Disease / Graves Ophthalmopathy / Graves’ orbitopathy (GO) / Gut microbiota / Heart rate / Helper cells / Humans / Immune system / Immunological tolerance / Immunoregulation / Intestinal microflora / Lactobacillus / Lymphocytes T / Mice / Microbiota / Microorganisms / Mimicry / Multiple sclerosis / Pathogenesis / Pathogens / Plasmids / Probiotics / Quality of Life / Receptors, Thyrotropin / Rheumatoid arthritis / Selenium / Th17 and Treg cells / Thyroid / Thyroid gland / Thyroid-stimulating hormone / Thyroid-stimulating hormone receptors / TSHR (thyroid-stimulating hormone receptor) / Vancomycin