Abstract
Hashimoto’s thyroiditis (HT) and alopecia areata (AA) are organ-specific autoimmune diseases that frequently co-occur, suggesting shared immunological and microbial pathways. The gut microbiome has emerged as a key modulator of immune function, yet disease-specific microbial signatures remain poorly defined. Fecal samples from 51 participants (HT: n = 16, AA: n = 17, healthy controls: n = 18) aged 18–65 years were analyzed using shotgun metagenomic sequencing followed by multivariate statistical analyses. While alpha and beta diversity did not differ significantly across groups, taxonomic profiling revealed disease-specific microbial patterns. Bacteroides fragilis was significantly enriched in HT, suggesting a potential role in immune modulation; although mechanisms such as polysaccharide A production and molecular mimicry have been proposed in previous studies, their involvement in HT remains to be confirmed. Microbacterium sp. T32 was elevated in both HT and AA, indicating its potential as a shared autoimmune marker. Functional analysis showed increased fermentation and amino acid biosynthesis in AA, contrasting with reduced metabolic activity and elevated carbohydrate biosynthesis in HT. HT and AA exhibit distinct gut microbial and metabolic signatures. Bacteroides fragilis and Microbacterium sp. T32 may serve as potential microbial correlates for autoimmune activity, offering new insights into disease pathogenesis and targets for microbiome-based interventions.