Characterisation of the Immuno-Metabolic Interface in Porcine Models of Nutritional Intervention

Abstract

There is increasing interest in the idea of using diet for health maintenance. Not only does dietary intake determine the availability of substrates for host metabolism, but it can also shape the composition of the intestinal microbiota, increasingly recognised as an ‘organ’ in its own right, which closely interacts with the mucosal immune system. Alterations in the mammalian-microbial-metabolic axis are associated with disease development and as such it is important to study the systemic consequences of dietary intervention on these interactions in an appropriate animal model such as the pig. The majority of the abundant metabolites present in porcine liver, kidney, serum and urine were assigned by one and two dimensional Nuclear Magnetic Resonance (NMR) spectroscopy and qualitatively compared; inter-compartmental differences in relation to mammalian-microbial co-metabolic representation were identified in the pig, and the applicability of NMR-based urinalysis to interrogate mammalian-microbial co-metabolism in this species confirmed. The initial weaning diet of pigs was found to initiate sustainable metabolic reprogramming in the young pig, leading to a persistent urinary metabolic signature after four weeks; this signature included metabolites linked to microbial metabolic processes and could indicate a diet-induced microbial reprogramming event at weaning. Differences in the initial weaning diet were also found to impact the metabolic and immunologic consequences of Bifidobacterium lactis supplementation on the young pig. The urinary metabolic profile from these animals was significantly correlated with patterns of intestinal mucosal immunoglobulin secretion and thus indicates the potential utility of biofluid-based metabolic profiling to assess mucosal responses to dietary intervention.