Bifidobacterium animalis subsp. lactis Probio-M8 enhances chondroitin efficacy for knee osteoarthritis in postmenopausal women via the gut-joint axis.

Abstract

UNLABELLED: Knee osteoarthritis (KOA) is a chronic joint disease marked by cartilage degradation and inflammation. Probiotics exhibit anti-inflammatory properties and may influence the gut-joint axis. Thus, a 4-month human trial was conducted to assess the adjunctive effects of Bifidobacterium animalis subsp. lactis Probio-M8 on KOA in postmenopausal women. Sixty-five KOA patients were randomly allocated to the probiotic group (n = 37; Probio-M8 and chondroitin sulfate) or placebo group (n = 28; placebo and chondroitin sulfate). Following a 3-month intervention, participants from both groups entered a 1-month observation without probiotic supplementation. Our findings revealed that Probio-M8 co-administration significantly reduced Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at months 1, 3, and 4 compared to the placebo group (P < 0.001). The probiotic group showed a significant decrease in serum IFN-γ and increases in IL-4 and IL-10 (P < 0.05). Fecal metagenome analysis showed significant changes in the gut microbiota of the probiotic group, with increases in potentially beneficial species, including Agathobaculum butyriciproducens, Bacteroides stercoris, B. animalis, Roseburia hominis, and Ruminococcus bromii, while Dorea formicigenerans decreased (P < 0.05). Changes in B. animalis were strongly associated with WOMAC scores. The gut metabolic potential analysis showed elevated levels of N-oleoylethanolamine and decreased levels of cholesterol and hypoxanthine in probiotic receivers (P < 0.05). Metabolite analysis revealed post-interventional alternations in fecal prostaglandin E2, stearic acid, cholic acid, chenodeoxycholic acid, xanthine, testosterone, and serum bile acids (P < 0.05). Collectively, Probio-M8 enhances the effectiveness of chondroitin sulfate in KOA management through modulating the gut-joint axis, potentially via regulating multiple inflammatory pathways. IMPORTANCE: The pathogenesis of knee osteoarthritis (KOA) and its phenotypic expression have been associated with the human gut microbiota. Our study demonstrated that the co-administration of Probio-M8 with chondroitin sulfate significantly alleviates KOA symptoms. This probiotic intervention enhances therapeutic efficacy through modulation of the gut microbiota and associated metabolic pathways, reducing inflammation and improving clinical outcomes. Our results underscore the potential of probiotic-driven therapies as an adjunctive treatment strategy and underscore the importance of the gut-joint axis in KOA management.