Noninvasive molecular fingerprinting of host-microbiome interactions in neonates.

The early postnatal period is a critical window for intestinal and immune maturation. Intestinal development and microbiome diversity and composition differ between breast- (BF) and formula-fed (FF) infants. Mechanistic examination into host-microbe relationships in healthy infants has been hindered by ethical constraints surrounding tissue biopsies. Thus, a statistically rigorous analytical framework to simultaneously examine both host and microbial responses to dietary/environmental factors using exfoliated intestinal epithelial cells was developed. Differential expression of ∼1200 genes, including genes regulating intestinal proliferation, differentiation and barrier function, was observed between BF and FF term infants. Canonical correlation analysis uncovered a relationship between microbiome virulence genes and host immunity and defense genes. Lastly, exfoliated cells from preterm and term infants were compared. Pathways associated with immune cell function and inflammation were up-regulated in preterm, whereas cell growth-related genes were up-regulated in the term infants. Thus, coordinate measurement of the transcriptomes of exfoliated epithelial cells and microbiome allows inquiry into mutualistic host-microbe interactions in the infant, which can be used to prospectively study gut development or, retrospectively, to identify potential triggers of disease in banked samples.