Dataset Information

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.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8137640 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of this study was to explore the effect of short-chain inulin on cecal microbiota of high-fat diet-fed leptin knockout mice and the different influences of cecal microbiota on wild-type and leptin knockout mice. A total of 18 specific pathogen-free male C57BL/6J wild-type mice and 18 C57BL/6J leptin knockout mice (OB/OB mice) were selected. Mice were divided into six groups according to their genotype: wild-type mice have three groups, including the normal diet group (CT), 60% high-fat diet group (CH), and 60% high fat with 10% short-chain inulin group (CHI); OB/OB mice were also divided into three groups, including the normal diet group (OT), 60% high-fat diet group (OH), and 60% high fat with 10% short-inulin group (OHI). The mice were fed for 8 weeks to analyze the diversity of cecal microbiota. The results show that compared with CH and OH, the variety of cecal microbiota was significantly reduced in CH and OH and further reduced in CHI and OHI. Bifidobacterium and Lactobacillus are the biomarkers in genus level. Dietary short-chain inulin significantly enhanced Bifidobacterium in OHI compared with OH (p < 0.01) and significantly reduced in CHI and compared with CH (p < 0.01). Lactobacillus was significantly enhanced in CHI and OHI compared with CH and OH, respectively (p < 0.01). Blautia was significantly enhanced in CH and OH compared with other groups (p < 0.01). Both Escherichia-Shigella and Enterococcus were significantly reduced in CHI and OHI, compared with CH and OH, respectively (p < 0.05). Escherichia-Shigella was even lower than CT and OT in CHI and OHI. Functional prediction of microbial communities showed that the abundance of amino acid sugar and nucleotide sugar metabolism pathways were significantly enhanced (p < 0.05) in CH and OH, and OH was significantly higher than CH (p < 0.05). Among the leptin knockout groups, PICRUSt2 function prediction showed that the fatty acid metabolism pathway significantly reduced (p < 0.05) in OHI and OT compared with OH. In conclusion, short-chain inulin modulated the dysbiosis induced by high-fat diet, improved probiotics growth and inhibited conditioned pathogenic bacteria, and the influences were significantly different in wild-type and leptin knockout mice.