Malic enzyme 3 mediated the effects of malic acid on intestinal redox status and feed efficiency in broilers

Abstract

Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increasing energy expenditure and therefore decreasing feed efficiency (FE). Several systems coordinately regulate redox balance, including the mitochondrial respiratory chain, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and different antioxidants. However, it remains unclear which redox balance compartments in the intestine are crucial for determining FE. In this study, we first screened the key targets of different metabolites and redox balance-related gene expression in broiler ceca. We then constructed a mouse colitis model to explore malic acid (MA) ability to alleviate intestinal inflammation. We further used controlled release technology to coat MA and investigated its effects on the intestinal redox status and FE in vivo. Finally, we examined the underlying mechanism by which MA modulated redox status using a porcine intestinal epithelial cell jejunum 2 (IPEC-J2) cell model in vitro. Our results demonstrated that the MA/malic enzyme 3 (ME3) pathway may play an important role in reducing oxidative stress in the broiler cecum. In addition, colon infusion of MA attenuated inflammatory phenotypes in the dextran sulfate sodium salt (DSS) induced mouse colitis model. Then, dietary supplementation with controlled-release MA pellet (MAP) reduced the feed to gain (F/G) ratio and promoted chicken growth, with reduced oxidative stress and increased bacterial diversity. Finally, the in vitro IPEC-J2 cell model revealed that ME3 mediated the effect of MA on cellular oxidative stress. In summary, our study firstly revealed the important role of the MA/ME3 system in the hindgut of broiler chickens for improving intestinal health and FE, which may also be crucial for the implications of colon inflammation associated diseases.