Mercury is a global contaminant, which may be microbially transformed into methylmercury (MeHg), which bioaccumulates. This results in potentially toxic body burdens in high trophic level organisms in aquatic ecosystems and maternal transfer to offspring. We previously demonstrated effects on developing fish including hyperactivity, altered time-to-hatch, reduced survival, and dysregulation of the dopaminergic system. A link between gut microbiota and central nervous system function in teleosts has been established with implications for behavior. We sequenced gut microbiomes of fathead minnows exposed to dietary MeHg to determine microbiome effects. Dietary exposures were repeated with adult CD-1 mice. Metabolomics was used to screen for metabolome changes in mouse brain and larval fish, and results indicate effects on lipid metabolism and neurotransmission, supported by microbiome data. Findings suggest environmentally relevant exposure scenarios may cause xenobiotic-mediated dysbiosis of the gut microbiome, contributing to neurotoxicity. Furthermore, small-bodied teleosts may be a useful model species for studying certain types of neurodegenerative diseases, in lieu of higher vertebrates.