Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice
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...
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| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-025-00766-y |
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| author | 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 |
| author_facet | 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 |
| author_sort | Song-xia Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-505d133ff6724f2d9d96857d4f31d441 |
| institution | Kabale University |
| issn | 2055-5008 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj-art-505d133ff6724f2d9d96857d4f31d4412025-08-20T03:46:07ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-07-0111111410.1038/s41522-025-00766-yGut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD miceSong-xia Zhang0Fang-fang Hu1Huan Chen2Jing Guo3Zhong-wen Xiang4Xin Ding5Meng-ling Ye6Wen-li Ye7Jun-hong Chen8Xin Wang9Wen-jing Han10Hong-hao Zhou11Wei Zhang12Yun Huang13Lie-lin Wu14Guang-hui Lian15Yao Chen16Department of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Hepatobiliary Surgery, Xiangya Hospital, Central South UniversityDepartment of organ transplantation, Xiangya Hospital, Central South UniversityDepartment of gastroenterology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1038/s41522-025-00766-y |
| spellingShingle | 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 Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice npj Biofilms and Microbiomes |
| title | Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice |
| title_full | Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice |
| title_fullStr | Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice |
| title_full_unstemmed | Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice |
| title_short | Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice |
| title_sort | gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ald mice |
| url | https://doi.org/10.1038/s41522-025-00766-y |
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