Tauroursodeoxycholic acid alleviates LPS-induced intestinal injury by reducing endoplasmic reticulum stress and...

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.