Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production
Uremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-11-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19490976.2020.1823800 |
| _version_ | 1818848980988067840 |
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| author | Yingyi Wang Jianping Li Chenkai Chen Jingbo Lu Jingao Yu Xuejun Xu Yin Peng Sen Zhang Shu Jiang Jianming Guo Jinao Duan |
| author_facet | Yingyi Wang Jianping Li Chenkai Chen Jingbo Lu Jingao Yu Xuejun Xu Yin Peng Sen Zhang Shu Jiang Jianming Guo Jinao Duan |
| author_sort | Yingyi Wang |
| collection | DOAJ |
| description | Uremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration, thus, delaying CKD progression. In the present study, we identified isoquercitrin (ISO) as a natural product that can perturb microbiota-mediated indole production without directly inhibiting the growth of microbes or the indole-synthesizing enzyme TnaA. ISO inhibits the establishment of H proton potential by regulating the gut bacteria electron transport chain, thereby inhibiting the transport of tryptophan and further reducing indole biosynthesis. This non-microbiocidal mechanism may enable ISO to be used as a therapeutic tool, specifically against pathologies triggered by the accumulation of the microbial-produced toxin IS, as in CKD. Herein, we have shown that it is possible to inhibit gut microbial indole production using natural components. Therefore, targeting the uremic toxin metabolic pathway in gut bacteria may be a promising strategy to control host uremic toxin production. |
| first_indexed | 2024-12-19T06:25:58Z |
| format | Article |
| id | doaj.art-79eb1592f4614facb99149dc03631853 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-19T06:25:58Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-79eb1592f4614facb99149dc036318532022-12-21T20:32:34ZengTaylor & Francis GroupGut Microbes1949-09761949-09842020-11-0112110.1080/19490976.2020.18238001823800Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin productionYingyi Wang0Jianping Li1Chenkai Chen2Jingbo Lu3Jingao Yu4Xuejun Xu5Yin Peng6Sen Zhang7Shu Jiang8Jianming Guo9Jinao Duan10Nanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineNanjing University of Chinese MedicineUremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration, thus, delaying CKD progression. In the present study, we identified isoquercitrin (ISO) as a natural product that can perturb microbiota-mediated indole production without directly inhibiting the growth of microbes or the indole-synthesizing enzyme TnaA. ISO inhibits the establishment of H proton potential by regulating the gut bacteria electron transport chain, thereby inhibiting the transport of tryptophan and further reducing indole biosynthesis. This non-microbiocidal mechanism may enable ISO to be used as a therapeutic tool, specifically against pathologies triggered by the accumulation of the microbial-produced toxin IS, as in CKD. Herein, we have shown that it is possible to inhibit gut microbial indole production using natural components. Therefore, targeting the uremic toxin metabolic pathway in gut bacteria may be a promising strategy to control host uremic toxin production.http://dx.doi.org/10.1080/19490976.2020.1823800gut microbiotachronic kidney diseaseuremic toxinindoxyl sulfateindoleisoquercitrin |
| spellingShingle | Yingyi Wang Jianping Li Chenkai Chen Jingbo Lu Jingao Yu Xuejun Xu Yin Peng Sen Zhang Shu Jiang Jianming Guo Jinao Duan Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production Gut Microbes gut microbiota chronic kidney disease uremic toxin indoxyl sulfate indole isoquercitrin |
| title | Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| title_full | Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| title_fullStr | Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| title_full_unstemmed | Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| title_short | Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| title_sort | targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production |
| topic | gut microbiota chronic kidney disease uremic toxin indoxyl sulfate indole isoquercitrin |
| url | http://dx.doi.org/10.1080/19490976.2020.1823800 |
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