Taurocholate mitigates LPS-induced intestinal barrier injury via host–microbiota and inflammatory pathway regulation

Sepsis is associated with dysregulated bile acid profiles, gut microbiota dysbiosis, and impaired intestinal barrier function. This study investigated the preventive effects and underlying mechanisms of taurocholic acid (TCA) against lipopolysaccharide (LPS)-induced systemic acute inflammation in mice using hematoxylin-eosin (HE), periodic acid-Schiff (PAS), qPCR, ELISA kits, 16S rRNA sequencing and GC-MS. TCA pretreatment (20 mg/kg TCA, TL20; 40 mg/kg TCA, TL40; 60 mg/kg TCA, TL60) mitigated the exacerbation of LPS-induced damage to physical, chemical, and immune barrier functions in the ileum and colon. The TL60 group showed significantly increased mRNA expression of ileal and colonic ZO-1 , ZO-2 , Claudin-1 , Occludin , SC , J chain , CD40 , PIgR , and IgA and protein expression of IgA, SIgA, IgG, and IgM in comparison with LCG group (p < 0.05). Notably, TCA upregulated mRNA expression of FXR and TGR5 , while suppressing the NF-κB pathway, suggesting a potential anti-inflammatory mechanism. Hepatic concentrations of TCA and taurohyocholic acid (THCA) were significantly lower in the LCG group than in the CG group but elevated in the colon; TCA pretreatment effectively prevented the abnormal accumulation of TCA and THCA in the colon (p < 0.05). Furthermore, TCA pretreatment significantly increased the relative abundance of bile acid-metabolizing genera in the colonic microbiota, including Desulfovibrio , Lactobacillus , Faecalibaculum , Bifidobacterium , Turicibacter , and Anaerostipes . These findings demonstrated that TCA pretreatment alleviates LPS-induced intestinal barrier injury and inflammatory responses by preventing intestinal barrier dysfunction, reducing bile acid retention, and modulating colonic microbial composition. • Taurocholic acid (TCA) pretreatment alleviates LPS-induced intestinal barrier injury in mice. • TCA enhances intestinal barrier integrity by inhibiting NF-κB signaling. • TCA modulates colonic microbiota such as Desulfovibrio , Lactobacillus , and Bifidobacterium .