Hologenomic Physiology of Livestock: Critical Integration of Gut Physiological Parameters, Neuroendocrine Signalling, and Immune Crosstalk in the Host–microbiome Unit

Abstract

The hologenome concept frames the host animal and its resident microbial communities as an integrated physiological and evolutionary unit, but its practical value in livestock depends on careful separation of demonstrated species-specific evidence from extrapolated mechanism. This critical narrative review synthesises evidence on host-microbiome-endocrine crosstalk in cattle, pigs and poultry, integrating gut physiological parameters, neuroendocrine signalling and immune regulation within a hologenomic framework. Literature was selected from accessible peer-reviewed sources and verified bibliographic records, with emphasis on studies relevant to livestock physiology, production stressors and microbial metabolites. Three convergent bodies of evidence are examined: the genetic architecture linking host genome and microbiome composition, expressed through microbiability and holobiability; neuroendocrine pathways, including hypothalamic-pituitary-adrenal axis activity, vagal afferent signalling and enteroendocrine hormone release; and immunological mediators, particularly short-chain fatty acids and tryptophan-derived metabolites, that couple microbial metabolism to mucosal and systemic immune tone. The evidence indicates that host genetic effects on the microbiome are generally modest, taxon-specific and best quantified in the bovine rumen. Associations between weaning, transport or heat load and concurrent shifts in microbial composition, barrier integrity and inflammatory markers are comparatively consistent, but causal inference remains strongest in limited livestock models, especially germ-free or infusion studies in pigs. Mechanistic detail on enteroendocrine, vagal and immunometabolic signalling remains disproportionately derived from rodent and human models. The review identifies methodological heterogeneity, cross-sectional design, taxonomic rather than functional profiling, and uneven species coverage as recurring constraints. Priorities include longitudinal multi-omic studies in defined production systems, direct livestock validation of receptor and vagal pathways, dose-response trials of metabolite-based interventions, and breeding-relevant quantification of microbiability for welfare and resilience traits. The findings support cautious, mechanism-informed development of microbiome-informed livestock management and selection strategies while underscoring the need for direct confirmation in target species.