Distinct gut microbiomic and metabolomic signatures in knee and hip osteoarthritis.

Abstract

Emerging evidence has suggested that distinct gut microbial profiles might differentially contribute to the development of knee and hip osteoarthritis (OA). The aim of current study was to identify gut microbial alteration and their potential functional consequences in primary knee and hip OA. Fecal and fasting plasma samples were collected from 24 knee OA, 24 hip OA, and 12 age, sex, and BMI matched OA-free controls. Gut microbiota were profiled by 16S rRNA gene sequencing, and plasma metabolomic profiling was performed. MaAsLin2 with ZINB model was applied to identify significantly differentially abundant taxa, which were then integrated with plasma metabolomic profiles to assess functional associations. Hip OA patients showed significantly lower α-diversity compared to controls (P<0.05), while β-diversity did not differ among groups. MaAsLin2 identified 4 microbial taxa differing between knee OA and controls, 6 between hip OA and controls, and 11 between knee OA and hip OA (P<7.48×10^-5). These taxa were correlated with 117, 247, and 189 metabolites, respectively (P<0.05), enriched in arginine biosynthesis, sphingolipid metabolism, and one carbon pool by folate. sPLS-DA showed that these metabolites moderately distinguished OA patients from controls. Gut microbiome and metabolome signatures in knee and hip OA exhibited both shared and joint-specific features, suggesting potential distinct microbiome-driven mechanisms in OA pathogenesis. These signatures were linked to inflammatory, amino acid, lipid, and vitamin metabolic pathways, underscoring the potential for personalized and joint-specific approaches in microbiome-based interventions.