Gut Microecology May Be Involved in the Pathogenesis of Hashimoto Thyroiditis by Reducing Production of Hydrogen Sulfide.

Abstract

Hashimoto thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis. This work aimed to illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels. We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomly assigned to 4 groups: experimental autoimmune thyroiditis (EAT) group, EAT + Healthy group, EAT + HT group, and EAT + HT + H2S group. 16S ribosomal RNA sequencing was performed to examine gut microbiota alterations and the H2S production pathway. Serum TgAb and H2S levels were assayed by enzyme-linked immunosorbent assay and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry. The gut microbiota was different after FMT among the EAT, EAT + Healthy, and EAT + HT groups. The thyroiditis score assessed by hematoxylin and eosin staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Helper T (Th1) and Th17 cell differentiation ratios were increased in the EAT + HT group compared to the other 3 groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Healthy group. H2S alleviated thyroiditis severity and related immune disorders, which were aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.