Correlation between Gut Dysbiosis, Metabolite Alterations and Erosive Hand Osteoarthritis - an observational study within the community-based Xiangya Osteoarthritis (XO) cohort.

Abstract

OBJECTIVES Erosive hand osteoarthritis (EHOA) is an aggressive subtype of hand osteoarthritis (HOA) with unclear pathogenesis. Since gut dysbiosis and related metabolite alterations may exacerbate inflammation and accelerate bone destruction, we investigated whether these abnormalities were involved in EHOA. METHODS Participants were drawn from the Xiangya Osteoarthritis Study. We compared gut microbial α-diversity and β-diversity between EHOA and controls (neither EHOA nor non-erosive HOA), and analyzed associations between microbial species abundance, functions, and EHOA. Targeted blood metabolomics were performed to identify microbiome-associated metabolites in EHOA. The associations between EHOA-related microbial species and blood metabolites were examine through multi-omics analyses. RESULTS Among 1,324 participants, significant differences in α-diversity (EHOA: median=4.53, non-HOA control: median=4.16; median difference=0.37 [95%CI: 0.09-0.57], P=0.016) and β-diversity (R²=0.002 [95%CI: 0.0018-0.006], P=0.015) were observed at the species level between EHOA and controls. Participants with EHOA had a higher relative abundance of Alistipes senegalensis (β coefficient:0.17 [95%CI:0.07-0.26]) and Fournierella massiliensis (β coefficient:0.39 [95%CI:0.28-0.49]). Tryptophan metabolism was the main altered metabolic pathway. Targeted blood metabolomics showed higher levels of L-5-hydroxytryptophan (β coefficient:0.38 [95%CI:0.15-0.61]), 3-indoleglyoxylic acid (β coefficient:0.35 [95%CI:0.01-0.69]), 5-hydroxyindoleacetic acid (β coefficient:0.27 [95%CI:0.09-0.45]), indoleacrylic acid (IA) (β coefficient:0.23 [95%CI:0.001-0.46]), and serotonin (β coefficient: 0.20 [95%CI: 0.004-0.40]), alongside lower levels of L-tryptophan (β coefficient:-0.41 [95%CI:-0.75 to -0.06]) and indole-3-acetyl-aspartate (β coefficient:-1.05 [95%CI:-1.79 to -0.32]) in EHOA. IA was positively correlated with EHOA-related microbial species, particularly Alistipes senegalensis (β coefficient:0.20 [95%CI:0.14-0.27]). CONCLUSIONS A higher relative abundance of Alistipes senegalensis and alterations in tryptophan metabolites, particularly higher levels of IA, are associated with EHOA.