Tauroursodeoxycholic acid alleviates LPS-induced intestinal injury by reducing endoplasmic reticulum stress and restoring Mucin2 in broilers

Abstract

Lipopolysaccharide (LPS)-induced intestinal inflammation in broilers is closely associated with endoplasmic reticulum (ER) stress and mucus barrier disruption. This study investigated the effects of tauroursodeoxycholic acid (TUDCA) on LPS-induced intestinal injury in broilers using a 2 × 2 factorial design with LPS challenge (0 or 1 mg/kg BW) and TUDCA administration (0 or 10 mg/kg BW). Ninety-six male Arbor Acres broilers were randomly assigned to four treatment groups, and intraperitoneal injections were administered from day 7 to day 9. Serum endotoxin and inflammatory cytokines were determined, along with ileal goblet cell density, Mucin2 content, and the gene expression of Mucin2. In addition, ER stress–related gene expression, particularly components of the PERK–eIF2α pathway, and ileal microbiota composition were evaluated. The results showed that LPS challenge significantly increased serum endotoxin and the concentrations of IL-1β, IL-8, and TNF-α, with significant LPS × TUDCA interaction effects detected (P < 0.05). TUDCA treatment reduced circulating endotoxin and these inflammatory cytokines across treatments (P < 0.05). LPS challenge significantly reduced ileal goblet cell density and decreased Mucin2 content and Mucin2 gene expression, whereas TUDCA treatment increased these indices (P < 0.05). LPS challenge increased the expression of ER stress–related genes, particularly Grp78, while significant LPS × TUDCA interactions were observed for Grp78 and eIF2α (P < 0.05). TUDCA treatment reduced IRE1 expression (P < 0.05) and tended to decrease PERK expression (P = 0.066). TUDCA significantly increased the relative abundance of Lactobacillus (P = 0.015), with a significant LPS × TUDCA interaction (P = 0.006). Correlation analysis revealed that Lactobacillus abundance was negatively associated with serum IL-1β, while IL-8 and TNF-α were positively correlated with ER stress–related genes (Grp78, PERK, and eIF2α), suggesting a link between inflammatory responses and ER stress activation in the ileum. In conclusion, TUDCA alleviated LPS-induced intestinal injury in broilers by improving mucus barrier function and modulating the transcription of ER stress-related genes, particularly those associated with PERK–eIF2α signaling. These effects were accompanied by an increase in Lactobacillus abundance, suggesting the potential of TUDCA for maintaining intestinal homeostasis under inflammatory conditions.