Gut microecology may be involved in the pathogenesis of Hashimoto's thyroiditis by reducing the production of hydrogen sulfide

Background: Hashimotos thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S), a microbiota-derived metabolite, also regulates immune function. Our previous research showed that the serum H2S levels of HT patients were significantly lower than those of healthy controls, and a reduced H2S synthesis capability by the intestinal microbiota was further found in feces from HT patients. Therefore, we speculated that an abnormal intestinal microbiota might have limited H2S production capacity, which impairs immunoregulation and promotes HT pathogenesis.Methods: We collected feces from HT patients and healthy donors for intestinal microbiota transplantation. Thirty seven female CBA/J mice were randomized into four groups: the experimental autoimmune thyroiditis (EAT) group, EAT + Health group, EAT + HT group, and EAT + HT + H2S group. 16S rRNA sequencing was performed to examine gut microbiota alterations. H&E staining of thyroid sections was used to evaluate EAT severity. Thyroglobulin antibody (TgAb) and H2S levels in serum were assayed by ELISA and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry.Results: The gut microbiota was different after fecal microbiota transplantation among the EAT, EAT + Health and EAT + HT groups. The number of mice with severe thyroiditis and the serum TgAb levels were higher in the EAT + HT group than in the EAT group, but H2S treatment reduced the number of mice with severe thyroiditis. Moreover, Th1 and Th17 cell differentiation ratios were increased in EAT + HT group mice compared to those in the EAT or EAT + Health group mice, and supplementation with H2S reversed this phenomenon. Furthermore, H2S levels were decreased in serum, and the dissimilatory sulfate reduction (DSR) pathway to produce H2S was attenuated in the EAT + HT group compared to that in the EAT + HT + H2S group.Conclusions: Gut microecology alteration contributed to the exacerbation of thyroiditis and related immune disorders in mice transplanted with fecal microbiota from HT patients. The attenuated the DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.