Protocatechuic acid attenuated inflammation caused by <i>Prevotella copri</i> 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 < 0.05), and reduced the expression of intestinal tight junction protein (p < 0.05). 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.