論文 - 詳細
| RRC ID | 59576 |
|---|---|
| 著者 | Pryor R, Norvaisas P, Marinos G, Best L, Thingholm LB, Quintaneiro LM, De Haes W, Esser D, Waschina S, Lujan C, Smith RL, Scott TA, Martinez-Martinez D, Woodward O, Bryson K, Laudes M, Lieb W, Houtkooper RH, Franke A, Temmerman L, Bjedov I, Cochemé HM, Kaleta C, Cabreiro F. |
| タイトル | Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. |
| ジャーナル | Cell |
| Abstract |
Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address the fundamental question of how gut microbes and nutrition, key regulators of host physiology, affect the effects of metformin. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we developed a high-throughput four-way screen to define the underlying host-microbe-drug-nutrient interactions. We show that microbes integrate cues from metformin and the diet through the phosphotransferase signaling pathway that converges on the transcriptional regulator Crp. A detailed experimental characterization of metformin effects downstream of Crp in combination with metabolic modeling of the microbiota in metformin-treated type 2 diabetic patients predicts the production of microbial agmatine, a regulator of metformin effects on host lipid metabolism and lifespan. Our high-throughput screening platform paves the way for identifying exploitable drug-nutrient-microbiome interactions to improve host health and longevity through targeted microbiome therapies. VIDEO ABSTRACT. |
| 巻・号 | 178(6) |
| ページ | 1299-1312.e29 |
| 公開日 | 2019-9-5 |
| DOI | 10.1016/j.cell.2019.08.003 |
| PII | S0092-8674(19)30891-8 |
| PMID | 31474368 |
| PMC | PMC6736778 |
| MeSH | Agmatine / metabolism Animals Caenorhabditis elegans / microbiology Cyclic AMP Receptor Protein Diabetes Mellitus, Type 2 / drug therapy* Escherichia coli / drug effects Escherichia coli / genetics Gastrointestinal Microbiome / drug effects* Host Microbial Interactions / drug effects* Humans Hypoglycemic Agents / pharmacology Hypoglycemic Agents / therapeutic use* Lipid Metabolism / drug effects Longevity / drug effects Metformin / pharmacology Metformin / therapeutic use* Nutrients / metabolism |
| IF | 36.216 |
| 引用数 | 20 |
| 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 | 217 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm1133 tm1108 |