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

IF 6.4 1区 生物学 Q1 BIOLOGY eLife Pub Date : 2024-11-07 DOI:10.7554/eLife.100068
Yang Fu, Xiao-Dan Luo, Jin-Ze Li, Qian-Yuan Mo, Xue Wang, Yue Zhao, You-Ming Zhang, Hao-Tong Luo, Dai-Yang Xia, Wei-Qing Ma, Jian-Ying Chen, Li-Hau Wang, Qiu-Yi Deng, Lukuyu Ben, Muhammad Kashif Saleemi, Xian-Zhi Jiang, Juan Chen, Kai Miao, Zhen-Ping Lin, Peng Zhang, Hui Ye, Qing-Yun Cao, Yong-Wen Zhu, Lin Yang, Qiang Tu, Wence Wang
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Abstract

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.

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宿主源植物乳杆菌通过改善肠道微生物群落和水解酶介导的嘌呤核苷降解,缓解高尿酸血症。
肠道微生物群与高尿酸血症(HUA)和痛风的发病机制有关。然而,寄居在宿主肠道中的益生菌(如乳酸杆菌)是否能预防 HUA 的发生仍不清楚。在此,我们从 HUA 鹅的盲肠中分离出植物乳杆菌 SQ001,并进行了尿酸(UA)和核苷共培养的体外试验。代谢组学和全基因组分析表明,该菌株可能通过其核苷水解酶基因促进核苷的吸收和水解。通过异源表达和基因敲除研究证实了 iunH 基因的功能作用。口服植物乳杆菌 SQ001 增加了乳酸杆菌的数量,降低了血清 UA 水平。此外,植物乳杆菌 SQ001 还能下调肝脏黄嘌呤氧化酶(参与尿酸合成的关键酶)和肾脏重吸收蛋白 GLUT9,同时增强肾脏排泄蛋白 ABCG2 的表达。我们的研究结果表明,植物乳杆菌具有改善HUA肠道微生物菌群失调的潜力,从而为其作为一种益生菌疗法应用于HUA或痛风患者提供了启示。
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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