Understanding the impact of neonatal glutamine supplementation on the interaction between gut epithelia, its mitochondria, and microbiota, and its importance for the development in low birthweight piglets

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With breeding for increasing litter size, approximately 10-20% of piglets within a litter are affected by low birthweight (LBW) and/or intrauterine growth restriction (IUGR), and the overall pre-weaning piglet mortality is up to 35%. This is ethically unacceptable, and grossly inefficient. Piglet LBW and IUGR are associated to lower postnatal growth, reduced intestinal size and maturity, impaired gut barrier function and mucosal immunity. It has been shown that increased intestinal permeability is associated with poor mitochondrial functions. Intake and composition of colostrum and milk play a major role in the stimulation and regulation of body and intestinal growth and development during early life as well as the functional maturation of the microbiome in suckling piglets. The microbiome releases metabolites that may affect host mitochondrial energy metabolism. In contrast to normal-weight litter mates, LBW and/or IUGR piglets have lower energy reserves and delayed access to colostrum intake immediately after birth, and thus, tailored nutritional solutions for young pigs might be a means to optimize gut health and development. One gut-friendly nutrient might be glutamine (GLN), which can improve intestinal and whole body growth and development, and prevent intestinal oxidative injury and inflammatory disease when given to piglets shortly before or after weaning. Thus a case was made for beneficial effects of additional GLN intake beyond its provision with milk, which might be particularly useful in this phase of life especially in IUGR piglets. There is suggestive evidence that the provision of additional dietary GLN could be beneficial to intestinal development, and mitochondrial function in suckling neonatal pigs. However, whether there is an interaction between GLN supplementation, intestinal microbiota, their metabolites and host mitochondria in suckling piglets which play a role for gut function is still poorly understood. The goal of the proposed collaborative research is to investigate whether early life GLN supplementation impacts the gut in a beneficial way. Moreover, we aim to understand the interaction of gut epithelium and its mitochondria with microbiota acutely and in the longer-term (after weaning). We will thus characterize the intestinal epithelium (mitochondria characteristics, proliferation, local defense mechanisms, amino acid and glutathione metabolism) and the microbiome composition and its metabolic activity at functional and molecular levels. In an overarching evaluation, we will determine components explaining the variation and delineate relationships between intestinal mitochondria transcriptome and microbiota, mitochondrial and intestinal trait complexes, microbiota and intestinal trait complexes, as well as GLN metabolism. We expect to elucidate how these interactions are associated with the development and health of neonatal piglets.