Bisphenol A bis(diphenyl phosphate) disrupts gut microbiota homeostasis and induces intestinal toxicity in zebrafish

Abstract

Bisphenol A bis(diphenyl phosphate) (BDP), a widely used oligomeric organophosphorus flame retardant, is widespread in environments and organisms. However, the toxicity of BDP remains largely unexplored. The intestine is an immune organ and is subjected to injury caused by contaminants. Here zebrafish were exposed to 0, 10 and 100 μg/L BDP for 21d, followed by another 21d of recovery, to investigate its intestinal toxicity. BDP altered the gut microbiota compositions with obvious changes in the abundance of phyla Proteobacteria and Fusobacteria, and genera Cetobacterium, Hydrogenophaga and Aeromonas, leading to intestinal dysbiosis. Consequently, distinct intestinal histopathological alteration was observed in the BDP-exposed zebrafish. The expressions of Claudin-1 and Mucin 2 decreased dose-dependently, whose disruption was persistent, indicating that BDP destroyed the barrier integrity and function of intestine. In addition, superoxide dismutase (SOD) and malondialdehyde (MDA), as well as the expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) increased, magnifying the occurrence of oxidative damage and inflammation. Significant correlation was found between the microbiota alteration and intestinal disruptions, suggesting that BDP-induced gut microbiota dysbiosis participates in the progression of intestinal injury. This study reveals the intestinal toxicity of BDP, and provides insights into its potential risks in organisms.