Dose-dependent biphasic effects of Eucommia ulmoides extract on growth performance and gut-microbiota-liver axis in largemouth bass ( Micropterus salmoides )

The intensification of largemouth bass aquaculture necessitates safe, efficacious feed additives to replace antibiotics. Eucommia ulmoides extract (EUE) exhibits phytogenic potential, yet its dose-response efficacy and gut-microbiota-mediated mechanisms remain unresolved in this species. A 120-day feeding trial was conducted with 990 juvenile largemouth bass randomly allocated to six dietary treatments: basal diet (control) or basal diet supplemented with EUE at 0.3‰, 0.6‰, 0.9‰, 1.2‰, or 1.5‰. Growth performance, hepatic antioxidant capacity, serum biochemistry, intestinal morphology, and gut microbiota were systematically evaluated. The results showed that the 0.9‰ EUE group achieved optimal outcomes: weight gain increased by 15.7% and FCR decreased by 14.3% compared with the control ( P < 0.05). Histologically, 0.9‰ EUE preserved the most compact hepatic lobular architecture with minimal lipid vacuolization, whereas concentrations ≥ 1.2‰ induced dose-dependent hepatocyte vacuolation and intestinal goblet cell hyperplasia, revealing a biphasic, hormesis-like dose-response. Serum biochemical profiling identified a distinctive “high-flux, high-clearance” metabolic phenotype at 0.9‰, characterized by peak concentrations of HDL, total protein, and cholesterol ( P < 0.05), indicating enhanced reverse cholesterol transport and protein anabolism. Intestinal morphometry demonstrated a “tall-and-dense” absorptive architecture in the 0.9‰ group, with significantly elevated villus height and the highest villus density among all treatments ( P < 0.05). Microbiota analysis revealed that 0.9‰ EUE selectively enriched Clostridium ⁠ ⁠ sensu ⁠ ⁠ stricto _1 (13.61% vs. <0.1% in the control and high-dose groups), a keystone genus implicated in bile acid biotransformation and short-chain fatty acid metabolism, suggesting a gut-microbiota-liver axis as the mechanistic driver. Paradoxically, the highest microbial diversity and richness occurred at 0.3‰, yet this did not translate into improved growth, challenging the prevailing “diversity-equals-health” paradigm in intensive aquaculture systems.