Towards screening the neurotoxicity of chemicals through feces after exposure to methylmercury or inorganic mercury in rats: A combined study using gut microbiome, metabolomics and metallomics

Mercury (Hg) is one of the chemicals that bring serious adverse effects to the environment and human beings. Methylmercury (MeHg) is a neurotoxin while inorganic Hg (IHg) is not. Early screening of the neurotoxicity of chemicals may help reduce the occurrence of neurological disorders by minimizing chemical exposure. This work proposed the combined application of gut microbiome, metabolomics and metallomics to differentiate the neurotoxicity between MeHg and IHg in rats. It was found that MeHg caused down-regulated Bacteroides, Firmicutes and Proteobacteria, and up-regulated Actinobacteria and Verrucomicrobia at phylum level, while MeHg caused up-regulated Verrucomicrobiaceae, Desulfovibrionaceae, Helicobacteraceae, Lachnospiraceae and down-regulated Rikenellaceae, Erysipelotrichaceae, Sutterellaceae, Anaeroplasmataceae and Coriobacteriaceae in feces than IHg did at family level; Besides, MeHg brought metabolites change in activation of gut-brain axis pathway than IHg did, such as Glutamate, γ-aminobutyric acid (GABA), Dopamine (DA) and Tryptophan. These differences between MeHg and IHg were further confirmed by the distribution of Hg in the intestine, as well as the level of brain-derived neurotrophic factor (BDNF) in the intestine, brain and serum. Therefore, the difference of toxicity between MeHg and IHg can be well distinguished through feces after exposure for only 24 h, which may be used for the screening of neurotoxicity of other chemicals.