Protocatechuic Acid Alleviates Intestinal Inflammation by Enriching Gut-Derived Lithocholic Acid to Suppress the TAK1/NF-ĸB/MAPK Pathway

This study demonstrated that the natural anti-inflammatory compound protocatechuic acid (PCA) effectively mitigates intestinal inflammation in piglets. PCA significantly suppressed interleukin (IL) -6 and Tumor Necrosis Factor-alpha (TNF-α) (P<0.05) and enhanced intestinal barrier integrity by upregulating tight junction proteins Occludin and ZO-1 (P<0.01).

Although not a direct regulator, PCA significantly inhibited the phosphorylation of TAK1 and its downstream kinases (P<0.05). 16S rDNA sequencing revealed that PCA altered the composition of the gut microbiota. Fecal microbiota transplantation (FMT) confirmed that PCA-remodeled microbiota alone could transfer the protective effect, reduced IL-6 and elevated Claudin-1 and ZO-1 in recipient mice (P<0.01). Targeted metabolomics identified a significant increase in secondary bile acids, particularly lithocholic acid (LCA), after PCA treatment (P<0.05).