A biotin-free diet attenuates the incidence of collagen-induced arthritis and alleviates microbial dysbiosis

Emerging evidence has shown that the gut microbiota and its products are important triggers in the pathogenesis of rheumatoid arthritis (RA). Biotin is a diet- and microbiome-dependent metabolite and an immune regulator; however, the role of biotin in RA remains unknown. In this study, we observed abnormal fecal biotin excretion in RA patients, which correlated with microbial alterations. Specifically, biotin content was inversely associated with gut microbial genera enriched in healthy controls, including Roseburia and Dorea. Meanwhile, it positively correlated with Oscillospira, which was highly enriched in RA individuals. Moreover, collagen-induced arthritis (CIA) mice fed a biotin-free diet had attenuated arthritis incidence with depressed differentiation of splenic CD3⁺ T cells and restored microbial diversities. The biotin-free diet also increased bone mass and protected against inflammation-induced bone loss in CIA mice. Additionally, the biotin-free diet reshaped the host metabolic phenotype of amino acids and microbial composition. Notably, biotin deficiency ameliorated the augmentation of Oscillospira in CIA mice. Collectively, our results suggested a potential link between biotin deficiency, gut microbiota dysbiosis and CIA progression.