The microbiota at the interface of environmental toxicants and the brain.

Abstract

Throughout life, humans are exposed to a diverse array of xenobiotics originating from diet, pharmaceuticals, and environmental contaminants. Positioned at the interface between the host and the external environment, the gut microbiota is uniquely situated to both sense and modify the effects of these exposures prior to systemic circulation and delivery to their host targets. Growing evidence indicates that the microbiota play critical roles in shaping xenobiotic fate through both direct metabolic transformation and modulation of host detoxification pathways, barrier integrity, and immune signaling. In this review, we summarize the impacts of disease-relevant environmental neurotoxicants on both the brain and microbial composition. We further integrate emerging mechanistic insights illustrating how microbiota-dependent processes can influence host toxicant responses and detoxification capacity, ultimately modifying exposure outcomes. Collectively, these findings position the gut microbiota as central mediators between environmental exposures and neurological health, providing a framework to better understand potential risk-modifying relationships.