Abstract: Objective: This study was conducted to investigate the effect of Enteromorpha prolifera polysaccharide (EP) on lipopolysaccharide (LPS)-induced intestinal barrier injury and the intestinal microbial composition in mice. Methods: Forty-eight 8-week-old C57BL/6J male mice were selected and randomly divided into four groups (12 mice/group): control (Ctrl), LPS, EP, and EP + LPS. The mice in the Ctrl and LPS groups were provided with a basal diet, and those in the EP and EP + LPS groups were given a basal diet supplemented with 600 mg/kg EP. After feeding for 28 days, the mice in the LPS and EP + LPS groups were injected intraperitoneally with 200 µL of LPS solution at a dose of 0.5 mg/kg body mass, and those in the Ctrl and EP groups were given the same dose of normal saline. Results: After 4 weeks of EP treatment, there was no significant change in LPS-induced liver damage or splenomegaly in mice (P > 0.05). Compared with the LPS group, EP treatment significantly reduced the serum levels of myeloperoxidase (MPO) (P < 0.05) and diamine oxidase (DAO) (P < 0.01), elevated the colonic gene expression of interleukin-1β (IL-1β) (P < 0.05), and decreased the colonic gene expression of inducible nitric oxide synthase (iNOS) (P < 0.05) and colonic Toll-like receptor 4 (TLR4) expression (P < 0.05). At the phylum level, EP treatment significantly increased the abundance of Verrucomicrobiota in mice with LPS-induced intestinal barrier injury (P < 0.01); at the genus level, it significantly decreased the abundance of Alloprevotella, Bacteroides and unclassified_o_Bacteroidales (P < 0.05) and increased the abundance of Lachnospiraceae_NK4A136_group, Anaerostipes and Akkermansia (P < 0.05). Conclusion: EP not only can prevent LPS-induced impairment of intestinal barrier function, but also can alleviate intestinal barrier damage in mice by regulating the expression of genes related to the TLR4 signaling pathway and the composition of the intestinal microbiota.

Key words: Enteromorpha prolifera polysaccharide; lipopolysaccharide; inflammation; intestinal barrier; gut microbes