論文 - 詳細
| RRC ID | 50616 |
|---|---|
| 著者 | Scott TA, Quintaneiro LM, Norvaisas P, Lui PP, Wilson MP, Leung KY, Herrera-Dominguez L, Sudiwala S, Pessia A, Clayton PT, Bryson K, Velagapudi V, Mills PB, Typas A, Greene NDE, Cabreiro F. |
| タイトル | Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans. |
| ジャーナル | Cell |
| Abstract |
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B6, B9, and ribonucleotide metabolism. Also, disturbances in bacterial deoxynucleotide pools amplify 5-FU-induced autophagy and cell death in host cells, an effect regulated by the nucleoside diphosphate kinase ndk-1. Our data suggest a two-way bacterial mediation of fluoropyrimidine effects on host metabolism, which contributes to drug efficacy. These findings highlight the potential therapeutic power of manipulating intestinal microbiota to ensure host metabolic health and treat disease. |
| 巻・号 | 169(3) |
| ページ | 442-456.e18 |
| 公開日 | 2017-4-20 |
| DOI | 10.1016/j.cell.2017.03.040 |
| PII | S0092-8674(17)30369-0 |
| PMID | 28431245 |
| PMC | PMC5406385 |
| MeSH | Animals Antineoplastic Agents / metabolism* Autophagy Caenorhabditis elegans Cell Death Colorectal Neoplasms / drug therapy Diet Escherichia coli / enzymology Escherichia coli / genetics Escherichia coli / metabolism* Fluorouracil / metabolism* Gastrointestinal Microbiome* Humans Models, Animal Pentosyltransferases / genetics |
| IF | 38.637 |
| 引用数 | 66 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 193 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | Keio collection |