Mucosal transcriptomic landscape along the small and large intestines in individuals with and without type 2 diabetes

Background A detailed mapping of functional differences among intestinal regions in healthy individuals remains incomplete. Identifying regional alterations in individuals with type 2 diabetes (T2D) could enhance our understanding of disease-related intestinal changes. Objective To characterise the transcriptomic landscape along the entire intestinal tract in healthy individuals and those with T2D, and to create a publicly accessible database for future research. Design In this observational study, mucosal biopsies were obtained from 16 sites along the intestinal tract through anterograde and retrograde double-balloon endoscopy in 12 individuals with T2D and 12 normoglycaemic matched healthy individuals. Full transcriptomic analysis was performed. Genes with significantly different expressions between intestinal regions were analysed in terms of their biological mechanisms in healthy individuals, while regional expression profiles were compared between individuals with and without T2D. Results In healthy individuals, distinct gene clusters in the small and large intestines were associated with processes including immune response, mitochondrial activity and metabolism of organic substances. Individuals with T2D exhibited alterations in immune system activity and barrier permeability in the ileocaecal region and the large intestine. Conclusion Our study offers a detailed mapping of the transcriptomic landscape in the human intestinal tract, demonstrating regionalised gene expression profiles tied to critical biological processes. Notable alterations in immune system activity in the large intestine were observed in individuals with T2D. The publicly available database generated from this study ( https://rnaseq.gubra.dk/ ) provides a valuable resource for exploring the mucosal transcriptome along the human intestinal tract. Trial registration number NCT03044860