Effects of black soldier fly larvae meal on hepatic metabolism and intestinal health in juvenile southern catfish (Silurus meridionalis): Insights from non-targeted metabolomics.

To investigate the effects of replacing fishmeal (FM) with black soldier fly larvae meal (BSFLM) on hepatic metabolism and intestinal health in juvenile southern catfish (Silurus meridionalis), six isonitrogenous and isoenergetic diets were formulated with graded replacement levels of 0%, 10%, 20%, 30%, 40%, and 50% and fed to fish for 8 weeks. Intestinal antioxidant parameters, serum immune factors, hepatic free amino acids, and non-targeted hepatic metabolomics were analyzed. No significant differences were observed among groups in intestinal superoxide dismutase (SOD), glutaredoxin (GSH-PX), total antioxidant capacity (T-AOC), or malondialdehyde (MDA) (ANOVA, all P > 0.05). Serum interleukin-10 (IL-10) showed a significant linear increase with increasing BSFLM inclusion (P = 0.021), indicating dose-dependent anti-inflammatory immunomodulation. Hepatic free amino acid profiling revealed that ornithine decreased significantly with increasing replacement (P = 0.012), S-adenosylmethionine (SAM) peaked in the H50 group (36.59 vs. 24.00 in H0, P = 0.006), proline decreased significantly (P = 0.030), taurine and cysteine were significantly elevated in the H50 group (P = 0.007 and 0.022, respectively), and gamma-aminobutyric acid (GABA) declined significantly (P = 0.004). Non-targeted metabolomics revealed a three-phase metabolic trajectory: 10-20% replacement represented an adaptation phase characterized by decoupling of central nitrogen metabolism from anabolism; 30% constituted a transition phase with synergistic integration of energy metabolism, carbohydrate utilization, and glucuronidation detoxification; 40-50% represented a stress/dysregulation phase, marked by a coordinated stress module containing norepinephrine and pyroglutamic acid, with 2-furoic acid emerging as a potential stress biomarker at 50% inclusion. The number of differentially abundant metabolites increased from 7 in the H10 group to over 60 in the H50 group. KEGG pathway enrichment confirmed activation of amino acid and secondary metabolite biosynthesis at low levels, while high levels enriched oxidative stress-related pathways including glutathione metabolism, ferroptosis, and ABC transporters. Collectively, these findings indicate that BSFLM replacement should not exceed 30% in juvenile southern catfish diets to balance sustainable protein utilization with maintenance of metabolic homeostasis and overall health.