Effects of Antibiotic-Induced Gut Microbiota Dysbiosis on Arsenic Bioaccumulation and Transformation in Mice and Its Potential Mechanisms

The gut microbiota plays a crucial role in arsenic (As) metabolism, yet the extent of As metabolism under gut dysbiosis and the gut’s response to As exposure remain lacking. This study used a mouse model with gut dysbiosis induced by cefoperazone to explore As bioaccumulation, transformation, and excretion. By integrating absolute quantification methods, this study monitored the responses of gut microbiota, As biotransformation genes (ABGs), and gut metabolites in mice exposed to 1 and 10 mg/L As. Arsenic accumulation in the liver, spleen, heart, ileum, and blood was markedly decreased in gut dysbiosis mice exposed to 10 mg/L As. These mice also exhibited lower proportions of DMA(V) and As(V) in the liver compared with normal mice. A total of 17 ABGs were detected in the mouse gut, with a significant reduction in their absolute abundance in gut dysbiosis mice (e.g., arsC, arsH, and arsB genes). Consistently, gut dysbiosis mice had lower bacterial loads, particularly for Alloprevotella and Bacteroides, accompanied by the upregulation of “amino acids” and “fatty acid esters.” Association analysis predicted several specific bacteria carrying ABGs, exemplified by Bacteroides carrying the arsC gene. Our findings provided further insights into As metabolism mediated by gut microbiota, for better understanding As-induced toxicity and disease risk.