ApcMin/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colon

• Published in: Scientific reports Vol. 10; no. 1; p. 13616
• Main Authors: Madhu, Basetti, Uribe-Lewis, Santiago, Bachman, Martin, Murrell, Adele, Griffiths, John R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.08.2020; Nature Publishing Group
• Subjects: 631/337; 631/45; 631/45/320; 692/4028; Alanine; Choline; Colon; Creatine; Cytosine; Deoxyribonucleic acid; DNA; DNA methylation; Duodenum; Glycine; Humanities and Social Sciences; Ileum; Jejunum; Leucine; Magnetic resonance spectroscopy; Metabolites; multidisciplinary; NMR; Nuclear magnetic resonance; Science; Science (multidisciplinary); Small intestine; Tumors; Valine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-70579-w

Topographical variations of metabolite concentrations have been reported in the duodenum, jejunum and ileum of the small intestine, and in human intestinal tumours from those regions, but there are no published metabolite concentrations measurements correlated with linear position in the mouse small intestine or intestinal tumours. Since DNA methylation dynamics are influenced by metabolite concentrations, they too could show linear anatomical variation. We measured metabolites by HR-MAS 1 H NMR spectroscopy and DNA cytosine modifications by LC/MS, in normal small intestines of C57BL/6J wild-type mice, and in normal and tumour samples from Apc Min/ + mice. Wild-type mouse intestines showed approximately linear, negative concentration gradations from the pylorus (i.e. the junction with the stomach) of alanine, choline compounds, creatine, leucine and valine. Apc Min/ + mouse tumours showed negative choline and valine gradients, but a positive glycine gradient. 5-Hydroxymethylcytosine showed a positive gradient in the tumours. The linear gradients we found along the length of the mouse small intestine and in tumours contrast with previous reports of discrete concentration changes in the duodenum, jejunum and ileum. To our knowledge, this is also the first report of a systematic measurement of global levels of DNA cytosine modification in wild-type and Apc Min/+ mouse small intestine.