Persistent fat malabsorption in cystic fibrosis; lessons from patients and mice

Abstract

Fat malabsorption in pancreatic insufficient cystic fibrosis (CF) patients is classically treated with pancreatic enzyme replacement therapy (PERT). Despite PERT, intestinal fat absorption remains insufficient in most CF patients. Several factors have been suggested to contribute to the persistent fat malabsorption in CF (CFPFM). We reviewed the current insights concerning the proposed causes of CFPFM and the corresponding intervention studies. Most data are obtained from studies in CF patients and CF mice. Based on the reviewed literature, we conclude that alterations in intestinal pH and intestinal mucosal abnormalities are most likely to contribute to CFPFM. The presently available data indicate that acid suppressive drugs and broad spectrum antibiotics could be helpful in individual CF patients for optimizing fat absorption and/or nutritional status.

The Cystic Fibrosis Intestine

“…Even in CF patients without clinical liver disease there is fecal loss of bile acids (O'Brien et al 1993), which can lead to poor micelle formation, contributing to fat and vitamin malabsorption. However, in CF mice fecal loss of bile salts does not appear to affect fat absorption (reviewed in Wouthuyzen-Bakker et al 2011).…”

CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

“…Respiratory and digestive systems are among the most CFtargeted organs, with consequences ranging from pancreatic insufficiency (27) and severe malnutrition (72) to pulmonary failure and ultimately death (43). Advances in medical management have considerably raised the life expectancy of CF patients, but this survival is unfortunately associated with the high prevalence of cystic fibrosis-related diabetes (CFRD), reaching up to 50% in CF adult subjects (48).…”

Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor

“…Part of the fat malabsorption in CF is independent of pancreatic enzyme activity [33,34]. When CFTR is dysfunctional, the intraluminal environment becomes more acidic, thus increasing the precipitation of bile salts, interfering with micelle formation and the action of transmembrane mucosal transporter proteins, and the fluidity of intestinal mucins [34].…”

“…When CFTR is dysfunctional, the intraluminal environment becomes more acidic, thus increasing the precipitation of bile salts, interfering with micelle formation and the action of transmembrane mucosal transporter proteins, and the fluidity of intestinal mucins [34]. When present in the small intestine, these factors likely interfere with absorption in patients with CF.…”

“…When present in the small intestine, these factors likely interfere with absorption in patients with CF. When present in the large intestine, they likely contribute to constipation and obstipation, common findings in patients with CF [34][35][36], which can diminish appetite [37]. Intestinal inflammation may also contribute to malabsorption and poor appetite.…”