Parabacteroides distasonis ameliorates ETEC-induced diarrhea in weaned piglets by regulating intestinal barrier function and intestinal inflammation

Abstract Enterotoxigenic Escherichia coli (ETEC) is the main pathogen causing bacterial diarrhea in piglets. Ningxiang piglets (native Chinese breed) has the characteristics of stress resistance and low diarrhea rate, which is closely related to the intestinal microbial structure shaped by its high fiber feed. Our study found that Parabacteroides distasonis ( P. distasonis ), a representative intestinal bacterial species in Ningxiang piglets, had a positive correlation with fecal secretory immunoglobulin A (sIgA). P. distasonis strain was isolated from Ningxiang piglets and verified the regulation on intestinal injury induced by ETEC in piglets. Results showed P. distasonis could alleviate the weight loss of piglets caused by ETEC infection. P. distasonis significantly decreased the diarrhea rate and inhibited the colonization of ETEC in intestinal mucosa, while decreased the ileal mucosal IL-1β, IL-6 and TNF-α levels after ETEC infection ( P < 0.05). P. distasonis decreased the serum DAO activity, D-lactate and Endotoxin and upregulating the expression of small intestine mucosal sIgA. P. distasonis enhanced the expression of tight junction proteins, including claudin-1, claudin-3, occludin, and zonula occludens-1 (ZO-1), at both the transcriptional and translational levels ( P < 0.05). It also upregulates the expression of intestinal epithelial proliferation markers including PCNA , β-catenin , CHGA , Lgr5 and LYZ ( P < 0.05). Furthermore, P. distasonis affected the microbial structure and increased the relative abundances of beneficial genera, as well as increased the SCFAs contents in ileum of ETEC-challenged piglets. Taken together, P. distasonis could maintain the integrity of intestinal epithelial barrier, alleviate intestinal inflammation and repair intestinal barrier damage caused by ETEC, which provides theoretical basis for nutritional intervention of diarrhea in piglets.