Investigating the Link between the Intestinal Microbiome and Th17/Treg Dysregulation in Hashimoto’s Thyroiditis, and the Therapeutic Potential of Vitamin D

Objective:

Autoimmune disease (AD) has become a leading cause of illness in the twenty-first century, with autoimmune thyroid disease at the forefront of these conditions. Hashimoto’s thyroiditis (HT) shares many features with other ADs, including associations with gastrointestinal symptoms linked to intestinal dysbiosis (ID). However, the pathogenesis of HT remains incompletely understood, particularly the role of specific T cell lymphocyte activity. The primary objective of this review was to investigate links between ID and HT pathogenesis, focusing on the relationship between a specific cluster of differentiation 4 (CD4) T cell subsets including T helper 17 (Th17) and regulatory T cells (Treg). A secondary aim was to explore whether vitamin D supplementation may serve as a viable intervention in managing HT, given existing research demonstrating links between Vitamin D status, HT pathogenesis and ID.

Methods:

A systematic literature search was conducted in PubMed using predefined inclusion/exclusion criteria across three tranches. A search of the review literature pertaining to thyroid autoimmunity, HT and the intestinal microbiome identified 21 papers for inclusion. A mechanistic literature search covering animal, in vitro and human studies on HT, autoimmunity, ID, intestinal microbiota, intestinal permeability (IP) and Th17 yielded 43 papers. A final search of human studies examining vitamin D status or supplementation in relation to ID, IP, Th17 and interleukin (IL)-17 identified 45 relevant papers. Accepted studies were critically appraised and synthesized in a narrative analysis.

Results:

Evidence across the included studies suggests an association between ID and pathogenesis of HT. Increased IP and alterations in Th17/Treg balance emerged as key contributing mechanisms. Vitamin D status was also associated with immune modulation, particularly involving Th17 activity, and was strongly linked to both ID and HT pathogenesis.

Conclusions:

ID may play a contributory role in HT pathogenesis through immune modulation involving CD4+ T cell subsets. Vitamin D supplementation demonstrates potential as an adjunctive strategy; however, further targeted human studies are required to clarify causality and therapeutic efficacy.