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

Abstract

Background Lactobacillus 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. Results Gene 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. Conclusion Collectively, 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.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model

“…Heterogeneous expression in E. coli and gene knockout in LGG demonstrated that these genes play different roles in nucleoside degradation. Similar to these findings, degradation function genes were also reported in Lactiplantibacillus plantarum , which catalyzed the hydrolysis of nucleosides into nucleobases in mice 21 . A recent study also showed that Clostridium sporogenes from human subjects has the pbuX gene for the conversion of UA to SCFAs 47 .…”

“…Recent research has demonstrated that some gut microbes participate in the mechanism of UA degradation. For example, the oral administration of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from fermented food has been shown to strongly degrade UA in mice 21 , 22 . Lactobacillus gasseri PA3 can decrease the UA concentration and increase the relative abundance of Lactobacillus 23 , 24 .…”

Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota

“…According to a study by He et al [17], inulin-type prebiotics were found to lower serum UA levels in patients with end-stage renal disease by increasing the degradation of UA in the intestinal microbiota. Studies have revealed that the ribonucleoside hydrolase in Lactobacillus can hydrolyze nucleosides into nucleobases in order to reduce the serum UA level in mice via the degrading of purine nucleosides and reducing purine absorption in the intestine [42,43].…”

A multi-omic assessment of the mechanisms of intestinal microbes used to treat diarrhea in early-weaned lambs

“…Paraffin sections of 5–8 mm were prepared from the paraffin-embedded tissue. Xylene ethanol dewaxed and hydrated the paraffin sections, and the dewaxed sections were stained with hematoxylin-eosin (H&E) solution ( 8 ).…”