Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.

Fecal microbiota transplantation (FMT) from disease-resistant Min pigs to DLY pigs alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in recipient piglets.

• FMT was performed from Min pigs (disease-resistant breed) to Duroc × Landrace × Yorkshire (DLY) pigs
• The study used 16S rRNA sequencing and metabolomics to investigate the relationship between transferred microbiota and disease resistance
• LPS-induced intestinal inflammation and barrier damage were both reduced following FMT
• The experimental approach combined in vivo piglet models with in vitro and mouse model validation

The gut microbiome of disease-resistant Min pigs converts bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA).

• Key bacterial genera and bile acid metabolites were identified through metabolomics analysis
• In vitro evidence demonstrated that the gut microbiome can convert primary bile acids to secondary forms
• UDCA was identified as the primary secondary bile acid produced by the microbiota conversion
• The identification was supported by combined 16S rRNA sequencing and metabolomics approaches

UDCA acts via the gut-liver axis on the farnesoid X receptor (FXR) to inhibit the PI3K/AKT/NF-κB signaling pathway.

• Mechanistic validation was performed in a mouse model
• UDCA's mechanism involves activation of the farnesoid X receptor (FXR)
• The PI3K/AKT/NF-κB pathway was inhibited downstream of FXR activation
• The gut-liver axis was identified as the route through which UDCA exerts its anti-inflammatory effects

UDCA treatment reduced inflammatory responses and preserved tissue structure in both the liver and colon.

• Tissue structural preservation was observed in both liver and colon in the mouse model
• Reduction of inflammatory responses was demonstrated following UDCA administration
• The protective effects were mediated through inhibition of PI3K/AKT/NF-κB pathways
• Both hepatic and colonic tissues showed structural protection, implicating the gut-liver axis

The study establishes a causal link between gut microbiota composition and disease resistance in pigs.

• The causal link was established by transferring microbiota from resistant Min pigs to susceptible DLY pigs via FMT
• The transferred microbiota conferred measurable protection against LPS-induced inflammation in recipient animals
• Targeting microbial bile acid metabolism is indicated as a strategy to restore intestinal and hepatic health
• The findings suggest that differences in secondary bile acid production, particularly UDCA, underlie breed differences in disease resistance