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

Fu, Y.; Luo, X.-D.; Li, J.-Z.; Mo, Q.-Y.; Wang, X.; Zhao, Y.; Zhang, Y.-M.; Luo, H.-T.; Xia, D.-Y.; Ma, W.-Q.; Chen, J.-Y.; Wang, L.-H.; Deng, Q.-Y.; Ben, L.; Kashif Saleemi, M.; Jiang, X.-Z.; Chen, J.; Miao, K.; Lin, Z.-P.; Zhang, P.; Ye, H.; Cao, Q.-Y.; Zhu, Y.-W.; Yang, L.; Tu, Q.; Wang, W.

doi:10.1101/2024.08.01.606206

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bioRxiv · 10.1101/2024.08.01.606206

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

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Abstract

AbstractGut microbiota has been considered to be associated with the development of hyperuricemia (HUA) and gout. Some prebiotics from different sources had the potential alleviation function in HUA. However, whether host-derived potential probiotics, like Lactobacillus, from the gut of HUA animals could prevent the development of HUA is still uncertain. In this study, we established a HUA geese model and isolated a Lactobacillus plantarum strain, SQ001, from the cecum of HUA geese. Nucleoside co-culture and metabolomics analyses revealed that L. plantarum SQ001 is involved in the absorption and hydrolysis of nucleosides. Whole genome analysis showed there are four genes related with nucleosides hydrolysis in L. plantarum SQ001. The function of iunH, a nucleoside hydrolase gene, was further confirmed by heterologous expression and knockout assays. Oral administration of L. plantarum SQ001 in HUA geese models upregulated the Lactobacillus abundance and reduced serum uric acid (UA) levels. Likewise, in mouse models, L. plantarum SQ001 increased the L. plantarum abundance and lowered serum UA levels by reducing hepatic UA synthesis protein XO and renal UA reabsorption protein GLUT9 expression, while increasing renal UA excretion protein ABCG2 expression. Our findings demonstrated that host-derived probiotics from geese could alleviate gut microbe dysbiosis and HUA in its host and mouse model. This study provides insights into the potential probiotic role of Lactobacillus plantarum in HUA or gout therapy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/606206v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@698e7eorg.highwire.dtl.DTLVardef@a2091org.highwire.dtl.DTLVardef@e0348aorg.highwire.dtl.DTLVardef@19958ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Fu, Y., Luo, X.-D., Li, J.-Z., Mo, Q.-Y., Wang, X., Zhao, Y., Zhang, Y.-M., Luo, H.-T., Xia, D.-Y., Ma, W.-Q., Chen, J.-Y., Wang, L.-H., Deng, Q.-Y., Ben, L., Kashif Saleemi, M., Jiang, X.-Z., Chen, J., Miao, K., Lin, Z.-P., Zhang, P., Ye, H., Cao, Q.-Y., Zhu, Y.-W., Yang, L., Tu, Q., Wang, W.. 2024-08-01. Host-derived Lactobacillus plantarum alleviates hyperuricemia by improving gut microbial community and hydrolase-mediated degradation of purine nucleosides. https://doi.org/10.1101/2024.08.01.606206

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