Studies on microbial programming in formula fed neonatal piglets and their susceptibility to Escherichia coli infection later in life

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Hyper-proliferacy in modern pig breeds has resulted in more frequent use of artificial rearing combined with feeding of bovine milk-based formula of piglets. Taking into account that the microbial colonization of the neonatal intestinal tract is mainly influenced by factors such as the environment and the diet, the hypothesis of this project is that artificial rearing and formula feeding represent early life stress factors, which i) affect the developing gut microbiota-host interplay and ii) increase the susceptibility to disease later in life. These hypotheses will be addressed in two experiments with newborn piglets. In a first experiment, the development of the small intestinal physiological reactions, the bacterial ecosystem and the innate and adaptive immune reactions of neonatal piglets during the first two weeks of life will be studied under the influence of different environments and diets using a factorial design. Therefore, piglets will be i) reared by the sow without formula supplementation, ii) reared by the sow and receive additional bovine milk-based formula, iii) reared in isolators and fed sow milk, or iv) reared in isolators and fed bovine milk-based formula. This design will allow distinguishing between the environmental and diet-induced effects, respectively. Jejunal activity of digestive disaccharidases (lactase, maltase, sucrase), morphological changes and mucin composition as well as intraepithelial, lamina propria and blood immune cell phenotypes will be characterized accompanied by analysis of gene expression of MUC genes and cytokines. The luminal and mucosa-associated microbiome will be characterized by deep sequencing of 16S rRNA and rDNA together with analysis of bacterial metabolites (D-/L-lactate, short chain fatty acids, biogenic amines, ammonium, phenols and indols). In addition, a metabolomics approach will be used to identify biomarkers in the serum and urine associated with different intestinal colonization patterns. In a second experiment, differentially raised piglets will be challenged after the weaning at the age of 21 days with an enterotoxigenic Escherichia coli strain and the mucosal and systemic reactions will be studied. It is anticipated that the project provides further insight into the effect of early intestinal colonization on host development and the disease susceptibility later in life. The results will have relevance for both animal health, but serve also as a model for human neonates.