The 4E approach to the Human Microbiome: Nested Interactions between the Gut-Brain/Body System within Natural and Built Environments

The human mind’s complexity and its interaction with the environment is one of the main epistemological debates throughout history. Recent ideas, framed as the 4E approach to cognition, highlight that human experience depends causally on both cerebral and extracranial processes, but also is embedded in a particular physical context and is a product of historical accumulation of trajectory changes throughout life. Accordingly, the human microbiome is one of the most intriguing actors modulating brain function and physiology.Here we present the 4E perspective to the Human Microbiome for understanding mental processes from a broader perspective, encompassing one's body physiology and environment throughout their lifespan, interconnected by microbiome community structure and dynamics. We review evidence supporting the approach and suggest the study of the global set of microbial ecosystem networks encountered by a person across their lifetime (from skin to gut to natural and built environments). We furthermore trace future empirical implementation of the approach. We finally discuss novel research opportunities and clinical interventions aimed towards developing low-cost/high-benefit integrative and personalized bio-psycho-socio-environmental treatments for mental health and including the brain-gut-microbiome axis.