Host-derived Lactobacillus plantarum alleviates hyperuricemia by improving gut microbial community and hydrolase-mediated degradation of purine nucleosides

The gut microbiota is implicated in the pathogenesis of hyperuricaemia
(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 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 Lactobacillus
plantarum SQ001 resulted in increased abundance of Lactobacillus species
and reduced serum uric acid levels. Furthermore, it down-regulated hepatic
xanthine oxidase (XO), a key enzyme involved in uric acid synthesis, as
well as renal reabsorption protein GLUT9, while enhancing the expression
of renal excretion protein ABCG2. Our findings suggest that Lactobacillus
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.

肠道菌群（gut microbiota）与高尿酸血症（hyperuricaemia, HUA）及痛风的发病机制密切相关。然而，宿主肠道内定植的乳杆菌属（Lactobacillus）益生菌能否预防高尿酸血症的发生，目前仍不明确。本研究从高尿酸血症鹅的盲肠中分离得到植物乳杆菌SQ001（Lactobacillus plantarum SQ001），并开展了尿酸与核苷共培养的体外实验。代谢组学与全基因组分析结果显示，该菌株可通过自身的核苷水解酶基因促进核苷的摄取与水解。通过异源表达与基因敲除实验，验证了iunH基因的功能。口服给予植物乳杆菌SQ001，可提升肠道乳杆菌属的丰度，并降低血清尿酸水平。此外，该菌株可下调肝脏中尿酸合成关键酶黄嘌呤氧化酶（XO）以及肾脏重吸收蛋白GLUT9的表达，同时上调肾脏排泄蛋白ABCG2的表达。本研究结果表明，植物乳杆菌可改善高尿酸血症相关的肠道菌群失调，为其作为益生菌疗法应用于高尿酸血症或痛风患者提供了新的研究思路与应用前景。