Biology of regional gut-mucosal-transcriptomes in healthy individuals and individuals with diabetic: incorporating cellular composition and embracing variation

Hannah Gilliam-Vigh and coworkers1 highlight that regional transcriptome differences are much larger than the difference between healthy and diseased individuals. Moreover, a substantially larger degree of regional difference was observed in the small intestine compared to the large intestine, inspiring separate intraregional transcriptome analyses for the small and large intestinal samples to enhance the resolution of detection of differentially expressed genes (DEG) in the large intestine. Clustering of regional transcription landscapes in the small intestine identified six distinct region-expression profiles that confirm expected regional distinctions of gut-metabolic and immune system-related functions. A striking example is the clear coincidence between the elevated expression of lipid catabolism processes in the small intestinal regions predominantly responsible for fat absorption (jejunum and early ileum). Likewise, expression of immune system associated pathways clearly peaked in the distal regions of the small intestine, colocalising with the known enrichment of Peyer’s patches and emphasising the predominant role of this part of the intestine in immune surveillance. Likewise, one of the four regional transcription clusters detected in the colon indicates a gradual increase in glycoprotein metabolism expression when progressing from caecum to rectum, …