Examination of Colonic Hypoxia in the UC Davis Type 2 Diabetes Rat Model
Type 2 diabetes is known to disrupt the composition of the gut microbiota; however, the exact mechanism that underlies this association has not been characterized. Colonocyte metabolism and its effect on luminal oxygen availability has recently been proposed as a mechanism by which the host can regulate commensal populations. Thus, our aim was to determine whether the progression of diabetes influences colonocyte oxygen levels in the UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rat, which spontaneously develops diabetes under normal chow feeding conditions. Age-matched male UCDT2M Rats (173.8 +/- 3.6 days) prior to the onset of diabetes (PD, n=15), within 1-month post onset (RD, n=12), and 3-month post onset (D3M, n=12) were included in this study. Rats were given an IP injection of pimonidazole (PMZ, 60mg/kg body weight) 1-hour prior to euthanization. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemistry detection of PMZ. Colon content microbiome was measured by 16S rRNA amplicon sequencing and content short chain fatty acids were measured by liquid chromatography-mass spectrometry.