Targeting dysbiosis of diabetes and colorectal cancer : Gut a feeling, it plays a role

Abstract

Introduction: In healthy individuals, the gut microbiota favors good butyrate-forming bacteria; this balance is shown to be revoked during diabetic-associated dysbiosis. Butyrate is a short chain fatty acid (SCFA) that acts as a histone deactylase inhibitor (HDAC) and is speculated to play a crucial role in mediating diabetic complications through inhibiting inflammation and ROS production. Previous work by our group demonstrated that ROS production is prevailing in the course of diabetes-associated complications. In this project we aim to study the role of diabetic and colorectal cancer dysbiosis and butyrate or probiotics on the development of diabetes-associated complications with a focus on diabetes and colon cancer onset and development. Methods: HT-29 were used in this project where proliferation via the viability assay was assessed. To confirm our in vitro observations, MKR and APC mice models were used. The effect of probiotics or butyrate supplement on the microbiota of the diabetic and the APC mice was assessed using biochemical and molecular techniques. After sacrifice, colons were harvested for biochemical, histological, and molecular analysis. Results: HT-29, colorectal cell line, were cultured either in 5mM media(Normal glucose; NG) or in diabetic mimicking media of 25mM (high glucose; HG). In parallel, experiment cells were treated with 0.75 mM butyrate in the presence or absence of HG. Butyrate treatment decreased HT-29 cellular proliferation starting at 12 hours and this was sustained throughout the whole length of the experiment. Furthermore, in animal models of diabetes and cancer, probiotics or butyrate treatment reversed the alteration seen in the autophagy pathway, where beclin-1 and LC-3β were comparable to that of control mice. By to by treatment with probiotics or butyrate reversed diabetes- and cancer-induced complications. Taken together, our results suggest that dysbiosis associated with both diabetes and colon cancer impair autophagy through oxidative stress and this can be r