Titanium dioxide nanoparticles (n-TiO 2 ) and bisphenol A (BPA) are 25 widespread environmental contaminants in the aquatic environment. We hypothesized 26 that n-TiO 2 may adsorb BPA, and thus modify its bioavailability and toxicity to 27 aquatic organisms. In this study, the bioavailability and toxicity of BPA (0, 2, 20, 200 28 µg/L) was investigated in the presence of n-TiO 2 (100 µg/L). n-TiO 2 sorbed BPA and 29 the resulting nanoparticles were taken up by zebrafish, where they translocated to the 30 liver, brain, and gonad tissues. Increased tissue burdens of both BPA and n-TiO 2 were 31 observed following co-exposure, and they also caused a reduction in plasma

To determine how environmental pollutants induce dysbiosis of the gut microbiota, we exposed adult zebrafish to model pollutants with varied modes of action (atrazine, estradiol, polychlorinated biphenyl [PCB]126, and PCB153) for 7 days. Subsequently, metagenomic sequencing of the intestines was performed to compare the gut microbiomes among the groups. We observed clear compound- and sex-specific responses to xenobiotic stress. Principal component analysis revealed involvement of the aryl hydrocarbon receptor (AhR) and, to a lesser extent, the estrogen receptor (ER) in the dysregulation of the intestinal microbiota. The model pollutants differentially impaired intestinal and hepatic physiological activities, as indicated by assessments of gut motility, epithelial permeability, inflammation, and oxidative stress. Correlation analysis showed that abnormal Aeromonas reproduction, especially in the PCB126 groups, was significantly positively associated with oxidative damage. Aeromonas closely interacted with Mannheimia and Blastococcus to regulate intestinal permeability. In summary, we demonstrated that ER and AhR signaling regulated the dynamics of the gut microbiota. Our findings provide new mechanistic insight into the complex interactions between the host metabolism and gut microbiota, which may contribute to the grouped assessment of environmental pollutants in future.

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