Genetic insights into the roles of fatty acids and gut microbiota in osteoarthritis: A Mendelian randomization study.

Traditional observational studies have shown that fatty acids and gut microbiota are crucial in osteoarthritis (OA) progression, but their findings are often conflicting due to biases, confounding factors, and measurement errors. We conducted a two-sample Mendelian randomization analysis using genome-wide association study data on fatty acids from 136,016 individuals, the gut microbiota from 7738 individuals, and osteoarthritis from 314,870 individuals. Elevated levels of total (odds ratio [OR]: 0.92; 95% CI 0.84-1.00; P = .039), saturated fatty acids (OR: 0.91; 95% CI 0.84-0.99; P = .034), and linoleic acid (OR: 0.92; 95% CI 0.85-1.00; P = .040) were associated with reduced OA risk. In terms of gut microbiota, Bifidobacterium adolescentis (OR: 0.89; 95% CI 0.80-1.00; P = .048) and Escherichia (OR: 0.90; 95% CI 0.81-1.00; P = .042) demonstrated protective roles against OA. Conversely, Oscillibacter (OR: 1.16; 95% CI 1.00-1.34; P = .043), Bilophila (OR: 1.28; 95% CI 1.07-1.54; P = .007), Erysipelotrichaceae (OR: 1.08; 95% CI 1.00-1.16; P = .044), and Bilophila within the Desulfovibrionaceae family (OR: 1.19; 95% CI 1.04-1.36; P = .012) were associated with an increased risk of OA. The findings indicate that modulating dietary factors and gut microbiota can independently reduce the risk and progression of OA, potentially improving the quality of life and health management in aging populations.