Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice

Abstract

Purpose Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

Gut Microbiota Characterization in Patients with Asymptomatic Hyperuricemia: probiotics increased

“…In this study, the abundance of the genus [Ruminococcus] and the genus [Eubacterium] in the population of the AH was very low. At present, the genus Ruminococcus and the genus Eubacterium are mentioned in the population of AH and the population of gout populations, which are similar to the results of this study [ 8 ]. In this study, the reduced bacteria in the AH population also had unidentified and unclassified bacteria with low abundance, such as unclassified_Enterobacteriaceae, unidentified_Ente-robacteriaceae, unidentified _ Lactobacillales , and unclassified_Enterococcaceae .…”

“…For example, common dietary components can be metabolized by the gut microbiota and produce metabolites that regulate host metabolism (such as dietary choline and trimethylamine). Some of these metabolites can have beneficial or harmful effects on the host [ 8 ]. Therefore, the study of the intestinal flora in patients with AH is a significant breakthrough in the study of disease pathogenesis.…”

Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts

“…Normally, approximately onethird of SU is excreted through intestinal uricolysis (41), indicating that gut microbiota may play an important role in metabolization of SU (e.g., Lactobacillus gasseri strains have the ability to decrease intestinal absorption of purines) (42). Studies have shown that Coprococcus may have beneficial effects through the production of short-chain fatty acids (SCFAs), the vital metabolites for the maintenance of intestinal homeostasis (43,44). For example, studies have demonstrated that 2 SCFAs (propionate and butyrate) provide ATP to the cells of the intestinal wall to promote UA excretion (45).…”

Impact of Camellia japonica Bee Pollen Polyphenols on Hyperuricemia and Gut Microbiota in Potassium Oxonate-Induced Mice

“…Hyperuricemia affected the composition and metabolites of the gut microbiota, especially short chain fatty acid (SCFA). Guo et al revealed the SCFA reduced in hyperuricemic mice [ 12 ]. However, few studies clarified the mechanism between the gut microbiota and hyperuricemia.…”