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内源性物质通过改善肠道微生物群落和水解酶介导的嘌呤核苷降解来缓解高尿酸血症。

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

机构信息

State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China.

State Key Laboratory of Microbial Technology, Shandong University, Shandong, China.

出版信息

Elife. 2024 Nov 7;13:e100068. doi: 10.7554/eLife.100068.

DOI:10.7554/eLife.100068
PMID:39508089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11542919/
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 , can prevent HUA development. Herein, we isolated 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 gene was confirmed via heterologous expression and gene knockout studies. Oral administration of SQ001 resulted in increased abundance of 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 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.

摘要

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,目前尚不清楚宿主肠道中存在的益生菌,如 ,是否可以预防 HUA 的发生。本研究从 HUA 鹅盲肠中分离出 SQ001,并在尿酸(UA)和核苷共培养物上进行了体外试验。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摄取和水解。通过异源表达和基因敲除研究证实了 基因的功能作用。口服 SQ001 可增加 物种的丰度并降低血清 UA 水平。此外,它下调了肝脏黄嘌呤氧化酶,这是一种参与 UA 合成的关键酶,以及肾脏重吸收蛋白 GLUT9,同时增强了肾脏排泄蛋白 ABCG2 的表达。我们的研究结果表明, 具有改善 HUA 相关肠道微生物失调的潜力,从而为其作为 HUA 或痛风个体的益生菌治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/ed3b1655b87c/elife-100068-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/944f5adfa763/elife-100068-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/2dbb0208d0ba/elife-100068-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/32cb91fd9935/elife-100068-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/6d57fb83efa1/elife-100068-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/f870f785ea54/elife-100068-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/25c98c32364f/elife-100068-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/c6191d2409bc/elife-100068-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/2cbe843b083b/elife-100068-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/ed3b1655b87c/elife-100068-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/944f5adfa763/elife-100068-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/2dbb0208d0ba/elife-100068-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/32cb91fd9935/elife-100068-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/6d57fb83efa1/elife-100068-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/f870f785ea54/elife-100068-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/25c98c32364f/elife-100068-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/c6191d2409bc/elife-100068-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/2cbe843b083b/elife-100068-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdc/11542919/ed3b1655b87c/elife-100068-fig11.jpg

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