Abstract:The gut microbiota plays a pivotal role in regulating animal health, and its structure and function can be significantly modulated by fermented feed. However, the lack of cross-species comparative studies has hindered a comprehensive understanding of the universal mechanisms underlying fermented feed-mediated microbial regulation.Objective To integrate multi-species data for deciphering cross-species regulatory patterns of fermented feed on gut microbiota and elucidating universal functional optimization and host-specific mechanisms.Methods We aggregated 464 gut microbiome datasets from pigs, cattle, chickens, and geese. The alpha/beta diversity analyses, linear discriminant analysis effect size (LEfSe), BugBase, and network analyses were employed to assess the diversity, differentially enriched genera, pathogenicity, and interactions of the gut microbiota.Results Fermented feed markedly reduced the alpha diversity of gut microbiota in monogastric animals (pigs, chickens, and geese) but not in ruminants (cattle). Although the beta diversity of gut microbiota remained statistically stable in different animals, fermented feed enriched probiotics (e.g., Lactobacillus and Faecalibacterium) while suppressing pathogens (e.g., Campylobacter and Brachyspira) to significantly diminish the pathogenic potential. Network analysis revealed enhanced connectivity, increased network density, reduced modularity, and improved community synergy in fermented feed groups. Host-specific responses were identified: Lactobacillus dominated in pigs, Akkermansia in cattle, and Flavonifractor in chickens.Conclusion Fermented feed modulates gut microbiota through a pattern coupling consistent response optimization with host-specific responses, selectively enriching keystone taxa to improve the specific function and reduce the pathogenicity. This study provides theoretical foundations for developing host-tailored fermented feed strategies.