Dysbiosis of gut microbiota by chronic coexposure to titanium dioxide nanoparticles and bisphenol A: Implications for host health in zebrafish

Gut microbiota is of critical relevance to host health. However, toxicological understanding of environmental pollutants on gut microbiota is limited, not to mention their combined effects. In the present study, adult zebrafish (Danio rerio) were exposed to titanium dioxide nanoparticles (nano-TiO₂; 100 μg/L), bisphenol A (BPA; 0, 2, and 20 μg/L) or their binary mixtures for three months. Sequencing of 16S rRNA amplicons found that nano-TiO₂ and BPA coexposure shifted the intestinal microbial community, interacting in an antagonistic manner when the BPA concentration was low but in a synergistic manner at a higher BPA concentration. Sex- and concentration-dependent responses to the coexposure regime were also observed for zebrafish growth and intestinal health (e.g. neurotransmission, epithelial barrier permeability, inflammation, and oxidative stress). Correlation analysis showed that oxidative stress after nano-TiO₂ and BPA coexposure was tightly associated with the imbalanced ratio of pathogenic Lawsonia and normal metabolic Hyphomicrobium, where higher abundance of Lawsonia but lower abundance of Hyphomicrobium were induced concurrently. A positive relationship was observed between zebrafish body weight and the abundance of Bacteroides in the gut, which was also closely associated with the genera of Anaerococcus, Finegoldia, and Peptoniphilus. This study revealed, for the first time, the combined effects of nano-TiO₂ and BPA coexposure on the dynamics of the gut microbiome, which proved to have toxicological implications for zebrafish host health. Nano-TiO₂ and bisphenol A coexposure disturbed gut microbiota dynamics and provides toxicological implications for host health in zebrafish.