Microbiome, Exposome, and Cognitive Development: The Known Unknowns

The gut microbiota, composed of trillions of microorganisms, plays a key role in bidirectional communication between the gut and brain, particularly during early life. The first two postnatal years represent a critical window when the exposome—the totality of all environmental exposures—shapes neurodevelopment via the microbiota–gut–brain axis. Exposome factors such as diet, birth mode, antibiotic use, infections, and xenobiotics can alter microbial composition and function, with downstream effects on immune signaling, neuroinflammation, and neurotransmitter production. These changes can influence neurodevelopmental trajectories and may contribute to disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder, though translation from animal models to humans remains challenging. Sex differences further modulate these interactions with mechanisms not fully understood. Integrating longitudinal exposome data with mechanistic insights is essential to clarify causal links and inform microbiome-based strategies to support cognitive development and reduce neurodevelopmental risk. Addressing the many “known unknowns” is key to priming brain health from early life onward.