Toward a gut-AMPK axis: the microbiome and AMPK signaling in nutrition and healthy aging

Modern nutrition research has evolved from early discoveries of essential vitamins to exploring the complex interactions between a much larger range of food-derived compounds (the foodome). The microbiome is a key link between diet and health outcomes through multiple gut-host axes. However, the field lacks a unifying framework to demystify its inherent complexities. This review outlines mechanistic evidence that the 5'-AMP-activated protein kinase (AMPK) is a potential mediator of host-microbe relationships and helps move towards the concept of a gut-AMPK axis. Further, it suggests that a plausible function of a "healthy" gut microbiome is to increase the bioavailability of metabolites capable of modulating AMPK. These insights can facilitate larger efforts to define what constitutes a functional gut microbiome, understand the health effects of the broader foodome, and support organismal resilience and healthy aging.