The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.
Keywords: Lactobacillus plantarum; hyperuricemia; infectious disease; microbiology; mouse; nucleoside hydrolase; purine.
Our blood contains many components, including waste products that need to be transported to the kidneys, where they can exit the body through urine. One such molecule, known as uric acid, forms when cells break down old DNA and other similar molecules. This process has several steps, with DNA being broken down into intermediate molecules called nucleosides before being converted into uric acid. If the amount of uric acid in the bloodstream becomes too high (a condition known as hyperuricemia), humans and other animals can develop high blood pressure, chronic kidney disease and other illnesses. Recent studies suggest that some types of ‘friendly’ bacteria living in the human gut may influence how uric acid levels are regulated. But the precise role these bacteria play remains unclear. Here, Fu, Luo et al. isolated one of these friendly bacterial species, known as Lactobacillus plantarum, from the gut of geese with hyperuricemia. The team grew the bacteria in the laboratory in two environments: one containing uric acid and the other containing nucleosides. The experiments revealed that while Lactobacillus plantarum does not directly act on uric acid, it does have enzymes that can convert nucleosides into other molecules. Further investigations, using whole-genome and metabolomic analyses, showed that Lactobacillus plantarum contains three genes encoding enzymes that act on a type of nucleoside known as a purine. Knocking out one of these genes prevented the bacteria from being able to convert purines into other molecules. Subsequently, Fu, Luo et al. demonstrated that Lactobacillus plantarum helps to mitigate the effects of hyperuricemia in geese and mice. These findings provide valuable insights into how microbes living in the gut regulate uric acid levels in their hosts. They may also inform future strategies for preventing and treating hyperuricemia in humans.
© 2024, Fu et al.