In food-producing animals, the gastrointestinal tract is an immunometabolic interface where nutrients, microbial communities, epithelial barriers, and mucosal immune systems converge to regulate nutrient utilization, barrier integrity, host defense, and physiological adaptation. This review critically evaluates how dietary inputs are translated through the diet–microbiota–host axis into intestinal phenotypes, host–microbiota responses, animal performance, and animal-food characteristics. Evidence from ruminants as well as non-ruminants is synthesized, with emphasis on studies in food-producing animals that directly evaluate dietary interventions and mechanistic investigations linking dietary substrates with microbial metabolism, epithelial–immune interactions, and host immunometabolic responses. Evidence from non-livestock models is considered primarily to clarify biological mechanisms and is distinguished from livestock outcomes. Evidence indicates that dietary modulation can alter microbial ecology and metabolite production, thereby influencing epithelial sensing, mucosal immune regulation, redox homeostasis, inflammatory signaling, and cellular metabolism. Microbial metabolites, including short-chain fatty acids, indole derivatives, and bile-acid metabolites, emerge as intermediates linking nutritional inputs with epithelial and immune function. These processes provide mechanistic connections between intestinal homeostasis, nutrient partitioning, stress resilience, and, in some experimental contexts, productive phenotypes and animal-product characteristics. However, the magnitude and direction of these responses are context dependent and vary with species, gastrointestinal anatomy, developmental or production stage, dietary composition, microbial community structure, and environmental challenge. Mechanistic and intervention evidence is more developed in swine and poultry, whereas extrapolation to ruminants requires consideration of foregut fermentation and altered delivery of substrates and metabolites to the intestine. Importantly, alterations in microbial composition, barrier markers, or immune signaling should not be interpreted as evidence of improved production performance or product quality unless these outcomes are directly demonstrated. The review therefore distinguishes established livestock evidence from mechanistic inference, association, and proposed biological frameworks, while identifying unresolved causal relationships between gut processes and whole-animal phenotypes. Emerging approaches, including microbiome profiling, multi-omics, sensor-based phenotyping, and artificial intelligence, may support biomarker discovery and nutrition decision-making, but their predictive and intervention value requires prospective validation across species and production environments. Overall, current evidence supports the gut as a regulatory interface between nutrition and host physiology, while highlighting species-specific, contextual, and causal limitations that constrain predictive precision nutrition.
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Shah et al. (2026) studied this question.
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