Abstract
Dietary habits and polyunsaturated fatty acids （PUFAs） significantly influence the pathophysiology of rheumatoid arthritis （RA）．This review summarizes our clinical and basic research exploring the therapeutic potential of PUFAs in RA. In a clinical study of RA patients, we identified that dietary patterns rich in 'Seafood' and 'Vegetables/Fruits' were significantly associated with lower disease activity.
Lipidomic analysis further focused our attention on epoxy fatty acids （EpFAs）， potent anti-inflammatory metabolites of PUFAs that are rapidly inactivated by soluble epoxide hydrolase （sEH）．We investigated the efficacy of combining an omega-3 PUFA-rich diet with an sEH inhibitor （TPPU） in a collagen-induced arthritis （CIA） mouse model. This combination therapy demonstrated a synergistic anti-arthritic
effect, significantly reducing joint inflammation and bone destruction compared to single interventions. Mechanistically, the effect was not mediated by suppressing autoantibody production. Instead, the combination treatment significantly altered the gut microbiota, specifically increasing the abundance of Lactococcus. Metabolic pathway analysis revealed an upregulation of Vitamin K biosynthesis, a nutrient known to inhibit osteoclastogenesis. These findings suggest that combining ω -3 PUFAs with sEH inhibition is a promising therapeutic strategy for RA. This approach leverages both the direct anti-inflammatory action of EpFAs and indirect benefits via modulation of the gut microbiota and vitamin K production, offering a novel foundation for integrated nutritional and pharmacological interventions.
