The role of the T helper 17 and T regulatory cell ratio in the gut-thyroid axis

Abstract

Alterations to the gut microbiota (GM) and its metabolites have been associated with Hashimoto’s Thyroiditis (HT) via modulation of T helper 17 (Th17) and T regulatory (Treg) cells. However, in comparison to other autoimmune diseases there is a shortfall in research investigating pathophysiological mechanisms. The aim of this review was to evaluate mechanisms linking the GM to the immune modulation of Th17 and Tregs in the context of HT.

A systematic literature search was undertaken in two tranches: 1) review papers; 2) primary human, animal and in vitro evidence. 80 papers met the inclusion criteria. Primary papers were critically appraised using SIGN50 and ARRIVE guidelines. Narrative analysis of the key mechanistic themes from primary studies was conducted and a network diagram was developed.

Th17 has a pathogenic phenotype but the context by which this conversion occurs is less well understood. Results suggested microbiota induced production of interleukin-6, interleukin-23 and serum amyloid A proteins play a role. However, downregulation of Tregs could be a prerequisite given their role in T effector cell suppression. Short-chain fatty acids may promote Treg activity; therefore, reduced levels could create a pathogenic environment. Translocation of lipopolysaccharides was indicated as a potential inducer of Th17. Evidence to support the migration of T cells primed in the intestines to other tissues also provided plausibility for mechanisms involving the gut-thyroid axis.

The findings suggest that the GM and its metabolites have immunomodulatory effects on the Th17/Treg ratio. However, research is lacking in HT patients and experimental thyroiditis animal models.