Transcriptomic and proteomic analysis of the jejunum revealed the effects and mechanism of protocatechuic acid on alleviating Salmonella typhimurium infection in chickens

Abstract

Salmonella typhimurium is a common cause of gastroenteritis, which infects animals and human. Protocatechuic acid has anti-inflammatory, immunoregulatory and anti-pathogenic effects, and is expected to be an effective choice for alleviating Salmonella infection and intestinal injury. A total of 180 1-d female, yellow-feathered chickens were randomly allocated into 3 treatment groups, the controls (Ctr), the Salmonella-challenged treatment (Sal) and the protocatechuic acid treatment (PA). Birds were fed a basal diet for 18 d, with birds in PA supplemented with 600 mg/kg protocatechuic acid. On 14 and 16 d, birds in Sal and PA were orally challenged with 109 CFU S. typhimurium, while birds in Ctr received an equal amount of PBS. The results showed that protocatechuic acid improved growth performance and jejunal structure in Salmonella-infected chickens (P < 0.05). In addition, protocatechuic acid suppressed (P < 0.05) the secretion of plasmal IgG, IL-1β, and IFN-β, and jejunal mucosal IL-6, IFN-β, complement protein 3 and 4. Mechanistically, the transcriptomic results showed that dietary protocatechuic acid inhibited acute inflammatory response and activated the signaling pathways of cytokine-cytokine receptor interaction, complement and coagulation cascades. Results of proteomic showed that protocatechuic acid inhibited the positive regulation of dendritic cell cytokine production and I-κB kinase/NF-κB signaling, as well as cytokine-cytokine receptor interaction and MAPK signaling pathways, and activated the mTOR signaling pathways. These results were critical to both suppressing the secretion of inflammatory cytokines and restoring the intestinal function. Dietary protocatechuic acid (600 mg/kg) was effective to alleviate Salmonella infection, as it suppressed the levels of cytokines and complement protein by inhibiting MAPK, I-κB kinase/NF-κB and enhancing the mTOR signaling pathway, thus offset the decline in weight loss and intestinal injury caused by infection.