Dietary high plant protein and high lipid impaired the intestine health of grouper by disrupting oxidative stress, immune response, and protein metabolism

This study aimed to investigate the molecular mechanisms underlying the detrimental effects of high lipid (HL) and high plant-protein (HP) diets on gut health in pearl gentian grouper, Epinephelus fuscoguttatus♂ × Epinephelus lanceolatus♀. Thus, grouper were randomly distributed into 12 plastic tanks, which were randomly assigned to four diet groups: control (C, 9.48 % lipid, 46.21 % protein), high lipid (HL, 16.70 % lipid, 46.37 % protein), high plant-protein (HP, 9.38 % lipid, 46.50 % protein), high lipid and high plant-protein (HLP, 16.67 % lipid, 46.54 % protein). After an 8-week feeding trial, the HL and HP treatments led to impaired growth performance, compromised gut structure, suppressed immune components, reduced antioxidant defense through the Keap/Nrf2 signaling, and inhibited protein metabolism via the PI3K/AKT/mTOR signaling. Notably, their combined effects (HLP) further exacerbated it. A significant decrease in the proportion of unclassified_Peptostreptococcaceae, Clostridium, and Curvibacter in all treatment groups. The Streptococcus, Lactobacillus, and Bosea were influenced by the interaction between dietary lipids and plant proteins. 14 metabolites that exhibited significant differences among all treatment groups, including arginine, prostaglandin B1, cortexolone, alpha-linolenic acid, and allocholic acid. The HL treatment primarily affected pathways related to lipid metabolism and immunomodulation, while the HP treatment predominantly influenced pathways associated with protein metabolism and immunomodulation. Our findings also indicated that the HP factor played a more prominent role in shaping the metabolic response of fish to the HLP intervention. Furthermore, a significant positive correlation between the Clostridium and the metabolites Cortexolone and Allocholic acid, while a negative correlation was observed between the Streptococcus, Lactobacillus, and Lactococcus and these metabolites. In conclusion, our study demonstrates that excessive inclusion of plant proteins and/or lipids negatively affects gut health in grouper by disrupting oxidative stress, immune response, and protein metabolism through modulation of the gut microbial-metabolite crosstalk.