The tolerance threshold of largemouth bass for starch in diet is below 8%. High-starch diet impairs energy metabolism, redox equilibrium, and immunological homeostasis via the "gut-liver" axis, further limiting the aquaculture of largemouth bass. To evaluate the efficacy of lactoferrin in alleviating the adverse effects of high-starch diet and its application in the healthy cultivation of largemouth bass.

Method The experiment was designed with four groups of isonitrogenous and isolipidic diets: 8% starch group (LS), 16% starch group (HS), and 400 mg/kg (HSL400) and 800 mg/kg (HSL800) lactoferrin groups based on HS. The largemouth bass (6.99±0.05 g) were fed for 70 days. The results indicated that, in comparison to the LS group, the WGR, SGR, and PER of the HS group were greatly diminished, while the FCR was markedly elevated; the growth performance (WGR, SGR, FCR, PER) of the HSL800 group bettered that of the HS group. Compared to the HS group, the HSL800 group exhibited greatly decreased serum levels of GLU, TG, and TC, as well as reduced ALT and AST activity. Additionally, the HSL800 group displayed a significant reduction in liver lipid accumulation, glycogen deposition, and vacuolization, along with decreased MDA levels and increased expression of sod and gsh-px. Compared with the HS group, the HSL800 group exhibited a significant increase in height and the number of intestinal villi, enhanced activities of protease and lipase, reduced levels of MDA, and decreased expression of pro-inflammatory factors il-1β, il-8, and tnf-α. Moreover, in contrast to the HS group, the expression levels of il-10, tgf-β1, claudin-1, occludin-1, and zo-1 were upregulated, whereas serum levels of D-Lac, DAO, and LPS were decreased in the HSL800 group. Furthermore, dietary lactoferrin increased the richness and evenness of the intestinal microbiota (ACE, Chao1 and Shannon), improved the health index of intestinal microbiota "(Firmicutes+Bacteroidetes+Actinobacteria)/Proteobacteria", increased the abundance of beneficial bacteria (Cetobacterium, Thiobacillus and others), and decreased the abundance of some potential harmful bacteria (Acinetobacter, Aeromonas and others) and Gram-negative bacteria. In conclusion, dietary lactoferrin can effectively alleviate the growth inhibition of largemouth bass caused by high-starch feed by improving liver and intestinal health. This study offers a theoretical foundation and technological specifications for the utilization of lactoferrin in the healthful aquaculture of aquatic organisms.