Integrated metabolomics and metagenomics reveal divergent caecal metabolic signatures following commercial gut health interventions in broilers.

BACKGROUND: The intensification of food production systems highlights the need for poultry gut health strategies aligned with One Health goals. Central to this is a balanced gut microbiota, which supports nutrient absorption, immunity, and disease resilience.

RESULTS: We applied integrative multi-omics, combining untargeted LC-MS metabolomics and shotgun metagenomics, to explore the caecal responses of commercial Ross-308 broilers to two widely used gut health interventions: ionophore supplementation (T1) and anticoccidial vaccination (T2). Across 7,554 detected metabolites, we identified candidate metabolic signatures: T1 was marked by trends in prenol lipids, including multiple soyasaponins, and enrichment of cellular stress-related pathways (e.g. glutathione pathway). T2 instead was associated with shifts in aromatic amino acid metabolism, elevating tryptophan-derived indoles such as 5-methoxyindole. While global metabolic profiles did not differ significantly (PERMANOVA p > 0.05), supervised integration (DIABLO algorithm) identified 405 potential metabolite-MAG correlations. Bacteroides fragilis emerged as a dominant associate, correlating positively with a diverse range of metabolites (n = 271). Functional gene analysis suggested a link between Mediterraneibacter spp. and soyasaponin deglycosylation, while Ruminococcaceae UBA3818 showed genomic potential for tryptophan utilisation and indole-linked metabolic steps.

CONCLUSION: Our exploratory findings suggest that prophylactic interventions impact the gut microbiome, resulting in divergent subsets of metabolic features. This highlights the potential of microbiome-informed strategies to improve enteric disease management and advance gut health centred approaches in both veterinary and human contexts.