Abstract
The intricate crosstalk between intestinal microbiota and host defense peptides (HDPs) in aquaculture has emerged as a cornerstone for advancing sustainable disease management and reducing reliance on antibiotics. This review synthesizes current insights into the bidirectional interactions shaping aquatic animal health, where HDPs, multifunctional immune molecules, directly neutralize pathogens while selectively modulating intestinal microbial communities to favor beneficial taxa (including Lactobacillus, Bacillus, Cetobacterium, Lactococcus, and so on) and suppress harmful species. Conversely, intestinal microbiota regulate HDP expression through microbial-derived signals, such as lipopolysaccharides and metabolites, which activate host immune pathways like Toll-like receptors (TLRs) to amplify innate defenses. This dynamic interplay underpins critical physiological functions, including nutrient absorption, intestinal barrier integrity, and systemic immune homeostasis, offering a dual mechanism to enhance disease resistance and growth performance. Practical applications, such as HDP-enriched feeds and probiotic-HDP synergies, have demonstrated efficacy in reducing mortality and improving productivity across species like shrimp, salmon, and carp. However, challenges such as HDP instability, species-specific variability in peptide efficacy, and the complexity of microbiota-HDP networks hinder broad implementation. Future research must prioritize innovative strategies, including engineered microbial systems for scalable HDP production, multi-omics approaches to unravel interaction mechanisms, and eco-friendly combinatorial therapies integrating HDPs, probiotics, and plant-derived compounds. By bridging immunology, microbiology, and aquaculture science, this field can transition toward antibiotic-free practices, ensuring ecological sustainability and global food security in the face of rising aquatic disease threats and environmental pressures.