Effects of 4-octyl itaconate and dimethyl fumarate on growth performance, intestinal microbiota, intestinal and hepatopancreas health of juvenile gibel carp (Carassius gibelio)

Abstract

Aquaculture needs effective antibiotic alternatives to control outbreaks of intestinal inflammation, as well as liver inflammation and metabolic disorder caused by enteritis. Specific metabolites have been shown to have immunomodulatory effects by the field of immunometabolism. As derivatives of the Krebs cycle metabolites, the itaconate and fumarate, 4-octyl itaconate (OI) and dimethyl fumarate (DMF) have recently attracted a lot of interest as anti-inflammatory medications. To evaluate the effects of oral administration of OI and DMF on fish growth and health, an 8-week feeding experiment followed by induction of enteritis with 2,4,6-trinitrobenzene sulfonic acid (TNBS) was carried out in gibel carp. The results showed that dietary 0.1%DMF improved the growth performance, and 0.1%OI up-regulated the abundance of beneficial intestinal microbiota. Both of OI and DMF alleviated intestinal inflammation by increasing intestinal anti-inflammatory cytokines, and relieved enteritis-induced hepatopancreas injury by inhibiting glycolysis both in vivo and in vitro. The 0.1%DMF also enhanced the tight junction and altered the microbiota to maintain the intestinal barrier. Collectively, dietary supplementation with 0.1% OI and DMF might be novel strategies to prevent enteritis and intestinal inflammation-induced hepatopancreas damage in gibel carp.