Decreased Expression of Enterocyte Nutrient Assimilation Genes and Proteins in the Small Intestine of Cystic Fibrosis Mouse

Objectives: Cystic fibrosis (CF) has major effects on the intestinal tract with potential consequences on nutrition, but these are not fully understood. I investigated the possibility of altered enterocyte maturation in CF, as suggested by decreased enterocyte nutrient assimilation gene expression in published transcriptome analysis of the small intestine of CF mouse. Methods: In CF and wild-type (WT) mice, enterocyte gene/protein expression was analyzed by quantitative realtime polymerase chain reaction (qRT-PCR), enzyme histochemistry, immunohistochemistry, and Western blot. One group of mice was maintained on a control liquid diet; to manipulate the gut microbiota, a second group was treated with oral antibiotics; to improve hydration of the gut lumen, a third group was given a laxative drinking solution. Results: On the control diet in the CF intestine, there were decreased levels (67%-85% reduction of WT levels) of enterocyte genes/proteins. Antibiotics did not normalize the expression of enterocyte markers in the CF mouse. In contrast, the laxative treatment of CF mice significantly increased expression to near WT levels. Conclusions: These studies suggest that the environment of the CF intestinal lumen plays a role in reduced maturation of enterocytes. Because changing the gut lumen environment can affect enterocyte maturation, this is not a cell-autonomous effect of loss of CF transmembrane conductance regulator.