PhD ceremony: Ms. M. Wouthuyzen-Bakker, 11.00 uur, Aula Academiegebouw, Broerstraat 5, Groningen
Dissertation: Cystic fibrosis and the gastro-intestinal tract
Promotor(s): prof. H.J. Verkade
Faculty: Medical Sciences
Cystic Fibrosis (CF) is a severe inherited disease that affects multiple organs of the human body, including the gastro-intestinal tract. In this thesis, we evaluated and ultimately aimed to improve several aspects of current treatment in CF care.
Our retrospective study with CF patients, who are in a relatively mild state of disease, illustrated that a high energy diet is probably not necessary in all CF patients to obtain an optimal nutritional status. In CF patients with a suboptimal nutritional status, correcting persistent fat malabsorption may, apart from a high caloric diet and supplementation with pancreatic enzymes, further improve the nutritional status. Literature showed that besides pancreatic insufficiency, several other gastro-intestinal abnormalities may contribute to the fat malabsorption in CF patients. Broad-spectrum antibiotics improved the nutritional status of CFTR knockout mice with small intestinal bacterial overgrowth, but not via improving the absorption of fat. Whether the same effect of antibiotics on the nutritional status can be expected in CF patients, should be further explored.
CF liver disease (CFLD) is currently treated with the bile salt ursodeoxycholic acid (UDCA). The effect of UDCA in CF conditions remaied debatable since in-vitro and ex-vivo studies indicated that its effect depends on CFTR. We demonstrated in mice in vivo that the effects of UDCA on bile flow and bile composition are maintained under CF deficient conditions. These results indicate that the therapeutic effects of UDCA are CFTR-independent and encourage the need for future studies in the treatment and/or prevention of CFLD. Finally, we showed that the severity of the gallbladder phenotype during CFTR deficiency is species-dependent, which is partially explained by the species-variation in the expression of calcium induced chloride channels. This finding strengthens the basis for exploiting pharmacological activation of these channels to prevent or mitigate the CF phenotype.
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