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

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.

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Publication Details

Journal
npj Biofilms and Microbiomes
Published
2025-07-14
DOI
https://doi.org/10.1038/s41522-025-00766-y
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Zhong‐Wen Xiang, Wei Zhang, Wenli Ye, Xin Wang et al.
npj Biofilms and Microbiomes
Gut microbiota and health
article

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

Zhong‐Wen Xiang, Wei Zhang, Wenli Ye, Xin Wang, Mengling Ye, Guoli Lian, Song-xia Zhang, Long‐Fei Wu, Yao Chen, Wenjing Han, Yun Huang, Honghao Zhou, Huan Chen, Jing Guo, Xinhua Ding, Fangfang Hu, Junhong Chen
article en

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.

npj Biofilms and MicrobiomesVol. 11(1)
Central South University (CN), Xiangya Hospital Central South University (CN)
National Natural Science Foundation of China, Central South University, Natural Science Foundation of Hainan Province, Xiangya Hospital, Central South University, Fundamental Research Funds for the Central Universities, Fundamental Research Funds for Central Universities of the Central South University
Zero hunger
Openalex Percentile: Top 85%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
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