Chronic exposure to tris(1,3-dichloro-2-propyl) phosphate: Effects on intestinal microbiota and serum metabolism in rats

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate ester that can adversely affect animal or human health. The intestinal microbiota is critical to human health. High-dose exposure to TDCIPP can markedly affect the intestinal ecosystem of mice, but the effects of long-term exposure to lower concentrations of TDCIPP on the intestinal flora and body metabolism remain unclear. In this study, TDCIPP was administered to Sprague-Dawley rats by gavage at a dose of 13.3 mg/kg bw/day for 90 days. TDCIPP increased the relative weight of the kidneys (P = 0.017), but had no effect on the relative weight of the heart, liver, spleen, lungs, testes, and ovaries (P > 0.05). 16 S rRNA gene sequencing revealed that long-term TDCIPP exposure affected the diversity, relative abundance, and functions of rat gut microbes. The serum metabolomics of the rats showed that TDCIPP can disrupt the serum metabolic profiles, result in the up-regulation of 26 metabolites and downregulation of 3 metabolites, and affect multiple metabolic pathways in rat sera. In addition, the disturbed genera and metabolites were correlated. The functions of some disturbed gut microbes were consistent with the affected metabolic pathways in the sera, and these metabolic pathways were all associated with kidney disease, suggesting that TDCIPP may cause kidney injury in rats by affecting the intestinal flora and serum metabolism.