Protocatechuic acid attenuated inflammation caused by Prevotella copri and its metabolites

Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. Prevotella copri (P. copri) showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous studies. To understand the underlying mechanism, a total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 108 CFU/kg P. copri or 1.0 × 108 CFU/kg P. copri +400 mg/kg PCA for 28 d. Results showed that P. copri decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G), with increased serum levels of interleukin (IL)-2 and IL-8 in piglets (p ), and reduced the expression of intestinal tight junction protein (p ). Dietary supplementation of PCA increased the ADG by suppressing inflammation and enhancing intestinal integrity. In vitro experiments demonstrated that argininosuccinic acid, indole-3-aldehyde, and N-acetylputrescine are critical metabolites produced by P. copri, which initiated inflammatory responses by upregulating pro-inflammatory cytokines and downregulating tight junction proteins in MODE-K cells. PCA was found to effectively attenuate these effects in a dose-dependent manner. In conclusion, PCA can improve the growth performance in weaned piglets by attenuating inflammation caused by P. copri and its metabolites.