Serum metabolomics and gut microbiota characterisation in patients with Sjögren disease complicated by anxiety disorder.

This single-centre cross-sectional study aimed to explore serum metabolomic and gut microbiota signatures in patients with Sjögren disease (SjD) complicated by anxiety disorder, with emphasis on microbe-metabolite crosstalk, to screen differential omics features and identify clinically relevant microbial and metabolic markers stratified by anxiety severity and SjD disease activity. A total of 59 SjD patients were enrolled, and all participants underwent serum untargeted metabolomics and faecal 16S rRNA gene sequencing. Participants were stratified according to the median Hamilton Anxiety Scale (HAMA) and European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) scores, and separate Pearson correlation analyses were performed between core clinical indicators and differential gut microbiota as well as serum metabolites. Five altered metabolites involved in purine and tyrosine metabolism were identified. SjD patients with anxiety exhibited enriched pro-inflammatory microbes and depleted anti-inflammatory commensals. Random-forest modelling identified Barnesiella, Lachnoclostridium and Veillonella as key discriminative genera; notably, Lachnoclostridium abundance showed a positive correlation with serum roccellic acid and N-(9-oxodecy) acetamide, indicating direct gut-circulating metabolite interplay. Subgroup analyses demonstrated gradient shifts of these core markers alongside increasing anxiety and disease severity, and Ligilactobacillus, Lachnoclostridium, xanthosine and 2,5-dihydroxybenzaldehyde were validated as anxiety-specific biomarkers. Collectively, SjD patients with anxiety display coordinated perturbations in serum metabolites and gut microbiota, and stratified correlation analyses yield novel microbiology-based, clinically interpretable biomarkers for identifying SjD patients complicated with anxiety disorder.