Exfoliated epithelial cell transcriptome reflects both small and large intestinal cell signatures in piglets

Assessing intestinal development and host-microbe interactions in healthy human infants requires noninvasive approaches. We have shown that the transcriptome of exfoliated epithelial cells in feces can differentiate breast-fed and formula-fed infants and term and preterm infants. However, it is not fully understood which regions of the intestine that the exfoliated cells represent. Herein, the transcriptional profiles of exfoliated cells with that of the ileal and colonic mucosa were compared. We hypothesized that exfoliated cells in the distal colon would reflect mucosal signatures of more proximal regions of the gut. Two-day-old piglets (n = 8) were fed formulas for 20 days. Luminal contents and mucosa were collected from ileum (IL), ascending colon (AC), and descending (DC) colon, and mRNA was extracted and sequenced. On average, ∼13,000 genes were mapped in mucosal tissues and ∼10,000 in luminal contents. The intersection of detected genes between three mucosa regions and DC exfoliome indicated an approximately 99% overlap. On average, 49% of the genes in IL, AC, and DC mucosa were present in the AC and DC exfoliome. Genes expressed predominantly in specific anatomic sites (stomach, pancreas, small intestine, colon) were detectable in exfoliated cells. In addition, gene markers for all intestinal epithelial cell types were expressed in the exfoliome representing a diverse array of cell types arising from both the small and large intestine. Genes were mapped to nutrient absorption and transport and immune function. Thus, the exfoliome represents a robust reservoir of information in which to assess intestinal development and responses to dietary interventions.