Potential involvement of the microbiota-gut-brain axis in the neurotoxicity of triphenyl phosphate (TPhP) in the marine medaka (Oryzias melastigma) larvae.

Triphenyl phosphate (TPhP), a prevalent pollutant in the aquatic environment, has been reported to induce neurotoxicity (e.g., a suppression in locomotor activity) in fish larvae, posing a great threat to fish populations. However, the underlying mechanism was not fully revealed. In this study, the Oryzias melastigma larvae (21 dph) were exposed to waterborne TPhP (20 and 100 μg/L) for 7 days and a decreased locomotor activity was found. After exposure, the brain transcriptome and communities of gut microbiota were investigated to explore the potential mechanism underlying the suppressed locomotor activity by TPhP. The results showed that 1160 genes in the brain were dysregulated by TPhP, of which 24 genes were identified as being highly associated with the neural function and development (including nerve regeneration, neuronal growth and differentiation, brain ion homeostasis, production of neurotransmitters and etc), suggesting a general impairment in the central nervous system. Meanwhile, TPhP caused disorders in the gut microbiota. The relative abundance of Gammaproteobacteria and Alphaproteobacteria, which can influence the brain functions of host via the microbiota-gut-brain axis, were significantly altered by TPhP. Furthermore, the Redundancy analysis (RDA) revealed positive correlations between the intestinal genera Ruegeria, Roseivivax and Nautella and the dysregulated brain genes by TPhP. These results suggest that TPhP might impair the central nervous system of the O. melastigma larvae not only directly but also through the microbiota-gut-axis (indirectly), contributing to the suppressed locomotor activity. These findings enrich our mechanistic understanding of the toxicity of TPhP in fish larvae and shed preliminary light on the involvement of microbiota-gut-brain axis in the neurotoxicity of environmental pollutants.