Microbiota-dependent in vivo biotransformation, accumulation, and excretion of arsenic from arsenobetaine-rich diet

Arsenobetaine (AB), a major organic arsenic (As) species in seafood, is regarded as safe by current regulatory assessments due to low toxicity and rapid unmodified urinary excretion. This notion has been challenged by reports of AB metabolism by intestinal bacteria in vitro and more recent evidence of in vivo AB metabolism in mice. However, these studies did not establish the causal role of intestinal bacteria in AB transformation in vivo . To address this, we employed gnotobiology and compared the biotransformation of As from naturally AB-rich rodent diet in mice that were either germ-free or colonized with gut microbiota of varying microbial diversity. Our results confirm the in vivo metabolism of AB in the intestine under chronic dietary exposure. The transformation of ingested As was dependent on the presence/absence and complexity of the gut microbiota. Notably, specific toxic As species were absent under germ-free condition. Furthermore, gut microbial colonization was linked to increased As accumulation in the intestinal lumen as well as systemically, along with delayed clearance from the body. These findings emphasize the mammalian gut microbiota as a critical factor in evaluating the safety of AB-accumulating seafoods. • Utilization of germ-free and gnotobiotic animal models to determine the role of gut microbiota in intestinal transformations of arsenobetaine in vivo. • Microbiota-dependent formation of highly toxic arsenicals in vivo. • Pervasive effects of microbial colonization and composition on arsenic speciation in the gut. • Gut microbial colonization increases local and systemic arsenic accumulation. • Gut microbiota as a key factor in assessing AB-containing food safety.