Dietary Nucleotides Improve Growth of Juvenile Eriocheir sinensis Under a Low-Fish Meal Diet via Enhanced Feed Intake and Gut Health

Fish meal replacement in aquaculture feeds requires supplementing functional additives to maintain animal performance. Nucleotides are a promising supplement in finfish, but their role in crustaceans remains poorly understood, particularly under challenging low-fish meal dietary conditions. This study evaluated dietary nucleotide supplementation effects on juvenile Chinese mitten crabs (Eriocheir sinensis) fed low-fish meal diets. Juvenile crabs (0.58 ± 0.01 g, first-year cohort) were distributed across 35 tanks with 1400 individuals total, creating seven dietary treatments (n = 5 replicates, 40 crabs per replicate). Over 56 days, crabs received either a control diet (35% fish meal) or six low-fish meal diets (15% fish meal) supplemented with graded nucleotide concentrations (0, 0.3, 0.6, 0.9, 1.2, or 2.4 g/kg). Nucleotide supplementation increased feed intake in a dose-dependent manner (p < 0.05); at 0.9 g/kg, intake was restored to the control level (p > 0.05). This higher intake coincided with increased digestive enzyme activities (α-amylase (α-Ams), trypsin (Try), and lipase) and improved growth (weight gain and specific growth rate; p < 0.05), with 0.9 g/kg or higher restoring growth to levels not significantly different from the high-fish meal control. Mechanistically, supplementation restored intestinal health by preserving morphology and lowering inflammation-related gene expression. Furthermore, it bolstered hepatopancreatic antioxidant defenses (a key transcriptomic finding) and favorably restructured the gut microbiota, which correlated with host performance (p = 0.007). Thus, nucleotide supplementation mitigates the adverse effects of low-fish meal diets by improving feed intake and intestinal health. The optimal level for growth was 0.85 g/kg based on broken-line regression.