Isoquinoline alkaloids enhance growth performance through multifaceted modulation of the bacterial-fungal microbiome, CAZyme profiles, gut health, and neuroendocrine function in broilers.

The bacterial-fungal microbiome and its carbohydrate-active enzyme (CAZyme) capacity play critical roles in regulating gut health and growth performance in broiler chickens. This study evaluated the effects of dietary isoquinoline alkaloids (IQ) on growth performance, gut microbiome composition, CAZyme profiles, and the microbiome-gut-neuroendocrine axis in broilers. A total of 400 Ross 308 (1-day-old) chicks were randomly assigned to either a Basal diet (CON) or IQ supplemented diet (IQ). Dietary IQ supplementation significantly increased final body weight and cumulative body weight gain (P < 0.0001) and improved feed conversion ratio (P < 0.05). Intestinal permeability was reduced (lower FITC-dextran; P < 0.05), accompanied by increased serotonin and serotonin-to-corticosterone ratio and decreased corticosterone (P < 0.05). Expression of inflammatory genes (TNF-α, NF-κB, IL-4, and TLR-1) was downregulated (P < 0.05). Microbiome analysis showed increased α-diversity (P < 0.05) and clear β-diversity separation (PERMANOVA, P < 0.001), with enrichment of beneficial bacteria (Akkermansia muciniphila, Lactobacillus salivarius, Turicibacter sanguinis, Bacillus subtilis) and suppression of fungal taxa (Aspergillus, Penicillium). CAZyme-related pathways involved in lignin and carbohydrate degradation were increased (P < 0.05). Microbial diversity was negatively correlated with inflammation and gut permeability, whereas network analysis identified 164 significant associations (|ρ| ≥ 0.50), revealing strong negative correlations between beneficial bacteria and inflammatory markers (ρ = -0.65 to -0.78) and positive associations for fungal taxa (ρ = 0.62-0.81). Serotonin was positively associated with microbial diversity (ρ = 0.63-0.70). In conclusion, IQ supplementation promotes a bacteria-dominant and metabolically active microbiome, reduces inflammation and intestinal permeability, and improves neuroendocrine balance, collectively enhancing gut health and growth performance in broiler chickens.