Bile acid metabolism and signaling in xenobiotic-induced liver injury. Attenuating effect of a selenium-enriched diet.

Abstract

Environmental exposure to complex chemical mixtures threatens metabolic health by disrupting the liver-gut microbiota axis. This study assesses a multi-pollutant cocktail (PC) comprising As, Cd, Hg, diclofenac and flumequine, on bile acid (BA) homeostasis in mice and evaluates the protective potential of dietary selenium. PC exposure induced mortality and body-weight loss despite sublethal individual doses, suggesting synergistic toxicity. Selenium supplementation, however, attenuated weight loss and partially reduced mortality. Hepatic profiling showed that antibiotic-induced microbiota depletion sharply reduced taurocholic acid, whereas PC exposure increased total hepatic BAs. However, selenium normalized total BAs and partially restored secondary species. Cholic acid remained stable, while PC exposure nearly depleted glycocholic and deoxycholic acids and increased taurodeoxycholic acid, a shift associated with colorectal and lung pathologies. These findings suggest xenobiotic-mediated disruption of BA conjugation and dysregulation of nuclear receptors, potentially predisposing to hepatic steatosis. Collectively, these findings support selenium as a nutritional strategy to mitigate antibiotic-induced dysbiosis and PC-induced hepatotoxicity, preserving metabolic integrity under chemical stress.