Thyroid Functional State-Dependent Dysbiosis of Gut Microbiota in Hashimoto's Thyroiditis: A Cross-Sectional Metagenomic Profiling Study

Background Hashimoto’s thyroiditis (HT) is a prevalent autoimmune thyroid disease (AITD) closely linked to genetic predisposition and environmental factors. Gut microbiota dysbiosis has recently been implicated as a critical contributor to AITDs’ pathogenesis. Our study aims to systematically investigate the dynamic alterations in gut microbial communities under varying thyroid functional statuses and elucidate their underlying mechanisms. Methods 67 HT patients with varying thyroid functional statuses and 23 healthy controls were enrolled. Fecal 16S rDNA sequencing and analyses (alpha diversity, LEfSe, correlation, functional pathways) assessed microbiota-thyroid function links. Results HT patients with hypo/hyperthyroidism had lower gut microbiota richness than euthyroid patients (more reduced in hyperthyroidism). The hyperthyroid group exhibited enrichment of Fusobacterium, the hypothyroid group was dominated by Clostridium sensu stricto_1, and the euthyroid group showed a predominance of short-chain fatty acid (SCFA)-producing bacteria (e.g., Lactobacillus). Clostridium sensu stricto_1 positively correlated with TPO-Ab levels but negatively correlated with FT3.Pro-inflammatory genera(e.g., Escherichia-Shigella, Streptococcus) demonstrated negative correlations with FT3.Functional prediction analysis revealed associations with L-tyrosine degradation in the hyperthyroid group, reduced proportions of bile acid metabolism pathways in the hypothyroid group, and enrichment of fatty acid metabolism pathways in the euthyroid group. Conclusions This study revealed that gut microbiota dysbiosis is closely associated with thyroid functional statuses in HT. Specific bacterial genera, such as Clostridium sensu stricto_1 and Fusobacterium, may contribute to immune regulation and disease progression. The dynamic alterations in gut microbial profiles provide potential biomarkers for precision diagnosis and treatment of HT.