Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract

Microbiome

Research

Filip Van Bockstaele¹  Zewang Guo²  Ruichen Gao²  Xiaoling Wu²  Hualing Cui²  Wenyong Lou²  Minhua Zong²  Zifu Ni²  Mengfan Li³ 

[1] Food Structure and Function Research Group (FSF), Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium;Lab of Applied Biocatalysis, School of Food Science and Engineering, South China University of Technology, Guangzhou, China;Lab of Applied Biocatalysis, School of Food Science and Engineering, South China University of Technology, Guangzhou, China;Food Structure and Function Research Group (FSF), Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium;

关键词: Hyperuricemia;    L. plantarum;    Gut microbiota;    Network analysis;    Serum uric acid;   

DOI  :  10.1186/s40168-023-01605-y

 received in 2022-12-08, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways.ResultsGene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and β diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA–C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage.ConclusionCollectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA–C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation.BbgstkDZoHsJm_QsUh-oZNVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 6

40517_2023_266_Article_IEq59.gif

40517_2023_266_Article_IEq57.gif

40517_2023_266_Article_IEq50.gif

40517_2023_266_Article_IEq45.gif