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 hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as <i>Lactobacillus</i>, can prevent HUA development. Herein, we isolated <i>Lactobacillus plantarum</i> 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 <i>iunH</i> gene was confirmed via heterologous expression and gene knockout studies. Oral administration of <i>L. plantarum</i> SQ001 resulted in increased abundance of <i>Lactobacillus</i> 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 <i>L. plantarum</i> 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.
Authors
- Muhammad Kashif Saleemi (ORCID: https://orcid.org/0000-0002-2329-7228)
- Daiyang Xia (ORCID: https://orcid.org/0000-0002-2688-6474)
- Wence Wang (ORCID: https://orcid.org/0000-0002-1753-7141)
- L.-N. Wang
- Juan Chen (ORCID: https://orcid.org/0000-0002-8006-0630)
- Qiang Tu (ORCID: https://orcid.org/0000-0002-8552-9485)
- Xiaodan Luo (ORCID: https://orcid.org/0000-0002-3225-502X)
- Kai Miao (ORCID: https://orcid.org/0000-0003-4832-3354)
- Lukuyu Ben
- Hao-Tong Luo
- Xue Wang (ORCID: https://orcid.org/0000-0001-8205-9468)
- Yue Zhao (ORCID: https://orcid.org/0000-0003-4046-9842)
- Lin Yang (ORCID: https://orcid.org/0000-0002-9080-8665)
- Wei-Qing Ma
- Zhen-Ping Lin
- Hui Ye (ORCID: https://orcid.org/0000-0001-7080-1442)
- Qingyun Cao (ORCID: https://orcid.org/0000-0002-0821-2097)
- Youming Zhang (ORCID: https://orcid.org/0000-0001-5403-4044)
- Jianying Chen
- Xianzhi Jiang
- Yongwen Zhu (ORCID: https://orcid.org/0000-0001-9842-9275)
- Qian-Yuan Mo
- Jinze Li (ORCID: https://orcid.org/0000-0001-6725-3318)
- Yang Fu
- Qiu-Yi Deng
- Peng Zhang
Institutions
- South China Agricultural University (CN)
- Shandong University (CN)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- University of Macau (MO)
- Poultry Research Institute (CN)
- Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (CN)
- State Key Laboratory of Microbial Technology
- University of Agriculture Faisalabad (PK)
Publication Details
- Journal
- eLife
- Published
- 2024-10-09
- DOI
- https://doi.org/10.7554/elife.100068
- Citations
- 27
- Primary Topic
- Gout, Hyperuricemia, Uric Acid
- Type
- article
- Field-Weighted Citation Impact
- 9.16
Funders
- China Agricultural Research System
- National Key Research and Development Program of China
- Basic and Applied Basic Research Foundation of Guangdong Province