From dietary exposure to organ injury: microbiome-mediated biotransformation of food-chain xenobiotics across the gut-liver-kidney axis.

Food-chain xenobiotics reach the intestine through food additives, processing-generated chemicals, environmental contaminants, and naturally occurring toxins. Their biological effects depend not only on intake but also on microbial metabolism and host handling. Gut microorganisms can detoxify parent compounds or generate metabolites with altered biological activity, while xenobiotic exposure can reshape microbial communities and host-microbial interactions. This review synthesizes evidence on these processes across the gut-liver-kidney axis, with particular attention to metabolic dysfunction-associated steatotic liver disease and chronic kidney disease. We examine direct microbial biotransformation alongside exposure-related changes in intestinal barrier function, immune responses, and metabolic signaling. The resulting synthesis highlights compound-specific and host-specific responses, shaped by microbial enzyme capacity, dietary context, barrier integrity, and hepatic and renal clearance. Impaired organ function can, in turn, alter microbial ecology and promote metabolite accumulation, creating bidirectional interactions between exposure and disease. Although experimental studies provide mechanistic insights, human evidence establishing causal links between dietary xenobiotics, microbial transformation, and chronic liver or kidney injury remains limited. We also evaluate the potential of integrated biomarkers, dietary interventions, and microbial enzyme-targeting strategies, identifying the evidence needed for clinical translation. Future progress requires longitudinal cohorts and controlled dietary studies that combine measured exposure, microbial function, metabolite profiles, and organ-specific outcomes. This integrated perspective provides a framework for investigating individual susceptibility to dietary xenobiotics and evaluating microbiome-informed approaches to food safety and nutrition.