The effect of polymeric formula on enterocyte differentiation
Exclusive Enteral Nutrition (EEN) is commonly used in the management of Crohn's disease (CD). Polymeric formulae (PF), comprising whole proteins along with the daily requirements of vitamins and minerals, are commonly used for EEN. The mechanism by which several weeks of PF treatment induces remission is incompletely understood and appears to be a combination of modulation of the intestinal microbiota and anti-inflammatory effects on the intestinal mucosa. These include a reduction in inflammatory cytokine production and improved barrier function.The hypothesis for the current work was that PF caused an increased rate of differentiation of enterocytes at physiological concentrations. This was tested using Caco-2 cell culture and murine enteroids as in vitro models of the intestine.When Caco-2 cells were treated with PF, it caused an increase in intestinal alkaline phosphatase (IAP) expression and activity, a marker of enterocyte differentiation. This was associated with a decrease in cell proliferation and viability. Murine enteroids dissociated after several hours of exposure to PF, possibly due to interference with Wnt signalling. It was hypothesised that the observed effect of PF on Caco-2 cells might be mediated via the vitamin D receptor (VDR). However, when the activity of this receptor was reduced through use of an inhibitor, no change in PF-induced IAP activity and/or decrease in proliferation was observed. This suggests that the VDR pathway is not the primary driver of the accelerated differentiation seen in PF-treated cells.
Advisor: Keenan, Jacqueline; Day, Andrew
Degree Name: Bachelor of Medical Science with Honours
Degree Discipline: Surgery
Publisher: University of Otago
Keywords: polymeric; formula; enterocyte; differentiation; Crohn's; disease; enteroid; intestinal; alkaline; phosphatase; vitamin; D; caco-2; butyrate; TEI-9647; enteral; nutrition; apoptosis; murine; crypts
Research Type: Thesis