Tris(1,3-dichloro-2-propyl) phosphate causes female-biased growth inhibition in zebrafish: Linked with gut microbiota dysbiosis

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is ubiquitous in aquatic environment, but its effect on intestinal health of fish has yet not been investigated. In the present study, the AB strain zebrafish embryos were exposed to environmentally realistic concentrations (0, 30, 300, and 3000 ng·L-1) of TDCIPP for 90 days, after which the fish growth and physiological activities were evaluated, and the intestinal microbes were analyzed by 16S rRNA gene high-throughput sequencing. Our results manifested that the body length and body weight were significantly reduced in the female zebrafish but not in males. Further analyses revealed that TDCIPP resulted in notable histological injury of intestine, which was accompanied by impairment of epithelial barrier integrity (decreased tight junction protein 2), inflammation responses (increased interleukin 1β), and disruption of neurotransmission (increased serotonin) in female intestine. Male intestines maintained intact intestinal structure, and the remarkably increased activity of glutathione peroxidase (GPx) might protect the male zebrafish from inflammation and intestinal damage. Furthermore, 16S rRNA sequencing analysis showed that TDCIPP significantly altered the microbial communities in the intestine in a gender-specific manner, with a remarkable increase in alpha diversity of the gut microbiome in male zebrafish, which might be another mechanism for male fish to protect their intestines from damage by TDCIPP. Correlation analysis revealed that abnormal abundances of pathogenic bacteria (Chryseobacterium, Enterococcus, and Legionella) might be partially responsible for the impaired epithelial barrier integrity and inhibition in female zebrafish growth. Taken together, our study for the first time demonstrates the high susceptibility of intestinal health and gut microbiota of zebrafish to TDCIPP, especially for female zebrafish, which could be partially responsible for the female-biased growth inhibition.