Gut microbial signatures in poultry under low-protein diets and lysine restriction: implications for precision nutrition.

Three key signatures - microbial, nutritional, and epigenetic - are pivotal in nutrigenomics, mediating poultry responses to nutritional signals, such as low-protein diets (LPDs) and lysine restriction (LR). These multidimensional signatures - encompassing bacterial, archaeal, and fungal taxonomy, functional genes, and metabolomic profiles (short-chain fatty acids; SCFAs) - orchestrate host metabolism, immunity, and feed conversion ratio (FCR). This PRISMA-ScR scoping review synthesizes multi-omics evidence showing that LPDs shift cecal fermentation toward saccharolytic pathways, enriching butyrate-producing taxa (Ruminococcaceae, Lachnospiraceae) while suppressing Proteobacteria and toxic proteolytic metabolites (ammonia, branched-chain fatty acids). LR elevates Actinobacteria/Synergistetes, triggers microbial nitrogen limitation, and reconfigures SCFA profiles through cross-feeding, thereby activating host nutrient sensors (mTOR downregulation, GCN2 upregulation) to prioritize immunity and FCR gains. Methanogenic archaea (Methanobrevibacter) fine-tune hydrogen economies, although diet-induced changes require deeper exploration. Key signatures forecast performance, featuring optimized Firmicutes/Bacteroidetes ratios and ureolytic genes (gdhA/glnA) as markers of protein resilience and profiles for breed-specific responses. SCFAs drive epigenetics (HDAC suppression, histone acetylation) and immunometabolism (Treg expansion, NF-κB dampening), bridging microbiome to host benefits via gut-liver interplay. Emerging applications span next-generation probiotics (NGPs) and live biotherapeutic products (LBPs), tailored from signature consortia (L. reuteri + B. velezensis) or archaeal agents, to sustain diet-induced states in antibiotic-free regimens. Major gaps persist in causal multi-omics validation, breed-specific responses, standardized baselines, and archaeal contributions. Integrating LPD/LR with tailored NGPs/LBPs promises precision nutrition strategies that enhance nitrogen utilization, reduce emissions, and improve welfare. Gnotobiotic, FMT, and AI trials are essential for translating microbial signatures into scalable flock-level precision management.