Integrative metabolomics and gut microbiota analyses reveal the protective effects of DHA-enriched phosphatidylserine on bisphenol A-induced intestinal damage

The protective effects of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS, 50 or 100 mg/kg) on bisphenol A (BPA)-induced intestinal damage were assessed. The biochemical indices, pathological examination, non-targeted metabolomics integrated with gut microbiota analysis, and immunofluorescence analysis were used to investigate the protective effects of DHA-PS and its underlying regulatory mechanism. The DHA-PS treatment improved the pathology of intestinal tract and increased the expression levels of Claudin-1, Occludin, and ZO-1. In addition, the DHA-PS treatment also notably decreased the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and increased the antioxidant enzymes activities. Moreover, DHA-PS treatment increased the relative abundances of Akkermansia, Alistipes, Butyricicoccus, Coriobacteriaceae_UCG-002, Enterorhabdus, and Lachnospiraceae_UCG-006. DHA-PS treatment alleviated BPA-induced intestinal damage by regulating the kynurenine pathway of tryptophan, lipid, and arachidonic acid metabolisms. Overall, this study suggested that DHA-PS could alleviate BPA-induced intestinal damage by enhancing the intestinal barrier integrity, improving gut microbial composition and metabolites, and inhibiting the TLR4/NF-κB pathways.