show Abstracthide AbstractOngoing efforts are directed at understanding the mutualism between the gut microbiota and the host in breast-fed versus formula-fed infants. Due to the lack of tissue biopsies, no investigators have performed a global transcriptional analysis of the developing intestine in healthy infants. As a result, the crosstalk between the microbiome and the host transcriptome in the developing mucosal-commensal environment has not been determined. In this study, we examined the host intestinal mRNA gene expression and microbial DNA profiles in full term 3 month-old infants exclusively formula fed (FF; n=6) or breast fed (BF; n=6) from birth to 3 months. Host mRNA microarray measurements were performed on intact sloughed epithelial cells in stool samples collected at 3 months. Microbial composition from the same stool samples was assessed by metagenomic pyrosequencing. Both host mRNA expression and bacterial microbiome phylogenetic profiles provided strong feature sets that classified the two groups of babies (FF and BF). To determine the relationship between epithelial cell gene expression and the bacterial colony profiles, the host transcriptome and functionally profiled microbiome data were analyzed in a multivariate manner. From a functional perspective, analysis of the gut microbiota's metagenome revealed that virulence characteristics differed between the FF and BF babies. Using canonical correlation analysis, evidence of multivariate structure relating eleven host immunity/mucosal defense-related genes and microbiome virulence characteristics was observed. These results, for the first time, provide insight into the integrated responses of the host and microbiome to dietary substrates in the early neonatal period.