Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.

Objective: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms.

Methods: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected.

Results: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity.

Conclusions: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.