Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy

Abstract

Cystic fibrosis (CF) is a progressive, genetic, multi‐organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF.

Effect of Modulator Therapies on Nutritional Risk Index in Adults with Cystic Fibrosis: A Prospective Cohort Study

“…In malnourished adolescents and adults with cystic fibrosis, conventional strategies of oral dietary supplements and dietary counseling are not known to cause a significant change in energy intake or ideal body weight percentage [ 3 ]. Despite the use of pancreatic enzyme replacement therapy, the frequency of malnutrition in CF suggests that aggressive nutritional support and highly effective CFTR modulator therapy are essential for a healthy BMI [ 4 , 5 , 6 ].…”

Special Issue: “Recent Advances in Ion Channels and Ion Channelopathies”

“…Cystic fibrosis (CF) is a progressive ion channelopathy caused by mutations in the CF membrane conductance regulator (CFTR) [13]. Much of our understanding of the pathological changes associated with CF has focused on lung dysfunction, however in addition, gastrointestinal dysfunction is also an important pathological feature in CF [14]. Nutritional status, because of gastrointestinal dysfunction, significantly impacts morbidity and mortality [15].…”