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Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract

BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we...

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Autores principales: Li, Mengfan, Wu, Xiaoling, Guo, Zewang, Gao, Ruichen, Ni, Zifu, Cui, Hualing, Zong, Minhua, Van Bockstaele, Filip, Lou, Wenyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354915/
https://www.ncbi.nlm.nih.gov/pubmed/37468996
http://dx.doi.org/10.1186/s40168-023-01605-y
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author Li, Mengfan
Wu, Xiaoling
Guo, Zewang
Gao, Ruichen
Ni, Zifu
Cui, Hualing
Zong, Minhua
Van Bockstaele, Filip
Lou, Wenyong
author_facet Li, Mengfan
Wu, Xiaoling
Guo, Zewang
Gao, Ruichen
Ni, Zifu
Cui, Hualing
Zong, Minhua
Van Bockstaele, Filip
Lou, Wenyong
author_sort Li, Mengfan
collection PubMed
description BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways. RESULTS: Gene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and β diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA–C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage. CONCLUSION: Collectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA–C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-023-01605-y.
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spelling pubmed-103549152023-07-20 Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract Li, Mengfan Wu, Xiaoling Guo, Zewang Gao, Ruichen Ni, Zifu Cui, Hualing Zong, Minhua Van Bockstaele, Filip Lou, Wenyong Microbiome Research BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways. RESULTS: Gene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and β diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA–C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage. CONCLUSION: Collectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA–C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-023-01605-y. BioMed Central 2023-07-19 /pmc/articles/PMC10354915/ /pubmed/37468996 http://dx.doi.org/10.1186/s40168-023-01605-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Mengfan
Wu, Xiaoling
Guo, Zewang
Gao, Ruichen
Ni, Zifu
Cui, Hualing
Zong, Minhua
Van Bockstaele, Filip
Lou, Wenyong
Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title_full Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title_fullStr Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title_full_unstemmed Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title_short Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
title_sort lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354915/
https://www.ncbi.nlm.nih.gov/pubmed/37468996
http://dx.doi.org/10.1186/s40168-023-01605-y
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