Distinct Gut Microbiomic and Metabolomic Signatures in Knee and Hip Osteoarthritis

Emerging evidence suggests that distinct gut microbial profiles might differentially contribute to the development of knee osteoarthritis (OA) and hip OA. The aim of this study was to identify gut microbial alteration and their potential functional consequences in primary knee OA and hip OA.

Fecal and fasting plasma samples were collected from 24 participants with knee OA, 24 participants with hip OA, and 12 age-, sex-, and BMI-matched OA-free controls. Gut microbiota were profiled by 16S ribosomal ribonucleic acid gene sequencing, and plasma metabolomic profiling was performed. Microbiome Multivariable Association with Linear Models 2 (MaAsLin2) with a zero-inflated negative binomial model was applied to identify significantly differentially abundant taxa, which were then integrated with plasma metabolomic profiles to assess functional associations.

Patients with hip OA showed significantly lower α-diversity compared with controls (P < 0.05), whereas β-diversity did not differ among the groups. MaAsLin2 identified 4 microbial taxa that differed 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), and were enriched in arginine biosynthesis, sphingolipid metabolism, and one-carbon pool by folate pathway. Sparse partial least squares discriminant analysis showed that these metabolites moderately distinguished patients with OA from controls.

Gut microbiome and metabolome signatures in knee OA and hip OA exhibited both shared and joint-specific features, suggesting 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, joint-specific approaches in microbiome-based interventions.