Metforminis the first-linetherapyfor 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 ofmetformin. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we developed a high-throughput four-wayscreento define the underlyinghost-microbe-drug-nutrientinteractions. We show that microbes integrate cues frommetforminand the diet through the phosphotransferase signaling pathway that converges on the transcriptional regulator Crp. A detailed experimental characterization ofmetformineffects downstream of Crp in combination with metabolic modeling of the microbiota inmetformin-treated type 2 diabetic patients predicts the production of microbial agmatine, a regulator ofmetformineffects 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.

Cell.2019 Aug 23. pii: S0092-8674(19)30891-8.

Doi: 10.1016/j.cell.2019.08.003.

“神药”二甲双胍抗衰老机制：依赖于特定的肠道菌代谢产物胍丁胺。