Indole-3-propionic acid enhances intestinal health and protects against Aeromonas hydrophila infection in high-fat-diet fed Nile tilapia (Oreochromis niloticus).

High fat diet (HFD) is widely utilized in aquaculture to promote growth and feed protein retention, but overconsumption of fat will induce systemic metabolic disorders of fish accompanied by impaired intestinal health and lower pathogen resistance. Indole-3-propionic acid (IPA) has been widely reported to enhance intestinal health in mammals. Our previous study has proven that IPA alleviated lipid metabolism disorder and lipotoxic liver injury in Nile tilapia (Oreochromis niloticus). However, it remains unclear whether IPA can sustain fish intestinal health. In this study, 540 Nile tilapia (2.53 ± 0.02 g) were allotted in 6 groups with 3 tanks each and fed with control diet or high-fat diet supplemented with different levels of IPA (0, 20, 40, 80, 160 mg/kg) respectively. After 8 weeks, it was observed that 80 mg/kg IPA proved the most beneficial for decreasing intestinal myeloperoxidase (MPO) enzyme activity and improving the survival rate of Nile tilapia infected with Aeromonas hydrophila. Dietary IPA restored intestinal barrier integrity impaired by HFD and increased the genes expression of tight junctional proteins (tjps), such as zona occludens 1 (zo-1) and occludin. The results showed that dietary IPA effectively mitigated HFD caused intestinal oxidative stress, manifesting as lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Dietary IPA promoted the gene and protein expression of aryl hydrocarbon receptor (Ahr) in intestine. Further investigation suggested that IPA could activate Ahr and affect nuclear factor-E2-related factor 2 (NRF2) signaling to reduce oxidative stress. Moreover, IPA might suppress enteritis by inhibiting the Ahr-mediated nuclear factor kappa light-chain-enhancer of activated B (NF-κB) signaling pathway. These findings indicated that IPA has the potential to improve intestinal health and pathogen resistance in HFD-fed fish, offering crucial insights for the application of innovative additives in aquatic feeds.