Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

npj Biofilms and Microbiomes Pub Date : 2025-07-14 DOI:10.1038/s41522-025-00766-y

Song-Xia Zhang, Fang-Fang Hu, Huan Chen, Jing Guo, Zhong-Wen Xiang, Xin Ding, Meng-Ling Ye, Wen-Li Ye, Jun-Hong Chen, Xin Wang, Wen-Jing Han, Hong-Hao Zhou, Wei Zhang, Yun Huang, Lie-Lin Wu, Guang-Hui Lian, Yao Chen

{"title":"Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice.","authors":"Song-Xia Zhang, Fang-Fang Hu, Huan Chen, Jing Guo, Zhong-Wen Xiang, Xin Ding, Meng-Ling Ye, Wen-Li Ye, Jun-Hong Chen, Xin Wang, Wen-Jing Han, Hong-Hao Zhou, Wei Zhang, Yun Huang, Lie-Lin Wu, Guang-Hui Lian, Yao Chen","doi":"10.1038/s41522-025-00766-y","DOIUrl":null,"url":null,"abstract":"<p><p>Drug tolerance is clinically common but its mechanism is unclear. Previous studies found RSV tolerance in ALD treatment. This study explores mechanisms involving gut bacteria and host factors. Male C57BL/6J mice were induced into ALD with the Lieber-DeCarli alcohol diet, then ALD-RSV group mice were gavaged RSV (150 mg/kg/day) for 5 weeks. Throughout the experiment, ALD and ALD-RSV mice were on the Lieber-DeCarli alcohol diet, while the Vehicle group received a control diet. By week 5, tolerance to RSV efficacy emerged, with markedly reduced RSV exposure at the final dose. ALD-RSV group exhibited increased levels of Eggerthella lenta (E.lent), which metabolizes RSV into dihydroresveratrol (DHR). Chronic RSV treatment upregulated UGT1A1, the enzyme converting RSV into its primary metabolite, trans-resveratrol-3-O-β-D-glucuronide (R3G). The synergy between gut bacteria and host factors enhances RSV metabolism in ALD mice, driving tolerance and offering insights into other clinical drugs tolerance mechanisms.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"11 1","pages":"132"},"PeriodicalIF":7.8000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259939/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Biofilms and Microbiomes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41522-025-00766-y","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Drug tolerance is clinically common but its mechanism is unclear. Previous studies found RSV tolerance in ALD treatment. This study explores mechanisms involving gut bacteria and host factors. Male C57BL/6J mice were induced into ALD with the Lieber-DeCarli alcohol diet, then ALD-RSV group mice were gavaged RSV (150 mg/kg/day) for 5 weeks. Throughout the experiment, ALD and ALD-RSV mice were on the Lieber-DeCarli alcohol diet, while the Vehicle group received a control diet. By week 5, tolerance to RSV efficacy emerged, with markedly reduced RSV exposure at the final dose. ALD-RSV group exhibited increased levels of Eggerthella lenta (E.lent), which metabolizes RSV into dihydroresveratrol (DHR). Chronic RSV treatment upregulated UGT1A1, the enzyme converting RSV into its primary metabolite, trans-resveratrol-3-O-β-D-glucuronide (R3G). The synergy between gut bacteria and host factors enhances RSV metabolism in ALD mice, driving tolerance and offering insights into other clinical drugs tolerance mechanisms.

查看原文本刊更多论文

肠道细菌和宿主协同作用促进白藜芦醇代谢并诱导ALD小鼠耐受。

药物耐受性在临床上很常见，但其机制尚不清楚。先前的研究发现，在ALD治疗中存在RSV耐受性。本研究探讨了肠道细菌和宿主因子的相关机制。采用Lieber-DeCarli酒精日粮诱导雄性C57BL/6J小鼠ALD，然后给ALD-RSV组小鼠灌胃RSV (150 mg/kg/d)，持续5周。在整个实验过程中，ALD和ALD- rsv小鼠采用Lieber-DeCarli酒精饮食，而Vehicle组采用对照饮食。到第5周，出现了对RSV的耐受性，最终剂量显著减少了RSV暴露。ALD-RSV组表现出将RSV代谢为二氢白藜芦醇（DHR）的Eggerthella lenta （E.lent）水平升高。慢性RSV治疗上调了UGT1A1，该酶将RSV转化为其主要代谢物，反式白藜芦醇-3- o -β- d -葡糖苷（R3G）。肠道细菌和宿主因子之间的协同作用增强了ALD小鼠的RSV代谢，促进了耐受性，并为其他临床药物耐受性机制提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.