Targeted blockade of IL-23 receptor by engineered IgY antibody attenuates bacterial enteritis via reprogramming gut microbiota-immune axis in grass carp (Ctenopharyngodon idella).

Abstract

Grass carp (Ctenopharyngodon idella), a key aquaculture species in China, is severely impacted by bacterial and viral infections, particularly A. hydrophila-induced enteritis, gill necrosis, and septicemia, necessitating sustainable alternatives to antibiotic-dependent disease management. In this study, an orally delivered anti-IL-23R IgY antibody (IgYIL-23R) was developed to attenuate bacterial enteritis in grass carp through dual modulation of gut immunity and microbiota. Microencapsulated IgYIL-23R (>1:8000 titer) was produced by immunizing hens with recombinant grass carp IL-23R and incorporated into fish diets (0.1-0.6&#xa0;%). Optimal growth performance was observed in the 0.3&#xa0;% IgYIL-23R group, with a 28.7&#xa0;% increase in final weight and a 1.8-fold elevation in specific growth rate (P&#xa0;<&#xa0;0.01). Concurrently, key pro-inflammatory genes (IL23R, IL-17, TNF-&#x3b1;) were suppressed by 60-75&#xa0;%, and intestinal histoarchitecture was restored. IgYIL-23R administration significantly altered gut microbiota composition, reducing pathogenic Proteobacteria (68&#xa0;%) and Aeromonas (82&#xa0;%) while enriching beneficial Bacteroidetes (3.2-fold) and Akkermansia (4.1-fold) (P&#xa0;<&#xa0;0.001). Upon challenge with A. hydrophila, fish fed 0.3&#xa0;% IgYIL-23R exhibited a 55&#xa0;% higher survival rate, minimal tissue damage, and enhanced metabolic functions, including antibiotic biosynthesis and &#x3b1;-linolenic acid metabolism. These findings demonstrate that targeted IL-23R blockade via oral IgY reprograms the microbiota-immune axis, providing a sustainable, antibiotic-free strategy for controlling enteritis in aquaculture.