Biodegradation of arsenobetaine to inorganic arsenic regulated by specific microorganisms and metabolites in mice

Arsenobetaine (AsB) is a primary arsenic (As) compound found in marine organisms. However, in mammals, the metabolic mechanism of AsB remains indistinct. Therefore, in this study, we investigated the biotransformation and regulatory mechanism of AsB, particularly the biodegradation process, in a mouse model to assess the underlying health hazards of AsB. We studied the biotransformation process of AsB in mice through the food chain [AsB feed-marine fish (Epinephelus fuscoguttatus)-mice (Mus musculus)]. Our results showed the significant bioaccumulation of total As, AsB, and, in particular, arsenate [As(V)] through biodegradation in mice tissues. As the abundance of Staphylococcus and Blautia (phylum, Firmicutes) increased, the expression of aqp7 (absorption) and methyltransferase (as3mt) (methylation) was upregulated. In contrast, the expression of S-adenosyl methionine (sam) (methylation) was downregulated. These findings suggest that demethylation and methylation occurred simultaneously in the intestines, with demethylation capacity being greater than that of methylation. Furthermore, Firmicutes such as Staphylococcus and Blautia showed a significant inverse relationship with arachidonic acid, choline, and sphingosine. Gene, microbiome, and metabolomics analyses indicated that Staphylococcus and Blautia and arachidonic acid, choline, and sphingosine participated in the degradation of AsB to As(V) in mouse intestines. Therefore, long-term AsB ingestion through marine fish consumption could cause potential health hazards in humans.