Cystic fibrosis from the gastroenterologist's perspective

Abstract

Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis.

The Microbiome and the Pathophysiology of Asthma

“…In bronchiectasis it is now believed that a change in composition of the lung microbiota through events such as antibiotic therapy and inflammation may have downstream consequences for the function of the immune system, allowing for the formation and preservation of chronic infection lead by microbial pathogens [25]. There is an appreciation that cystic fibrosis is a multisystem disease with involvement of the hepatobiliary and gastrointestinal tracts [26]. While gastrooesophageal reflux (GOR) effects CF patients, the lung and gastric microbiomes and an inter-dependant relationship between the two is clearly defined.…”

A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease

“…CF is the most frequent monogenic lethal disease worldwide (Cutting, ) , caused by loss‐of‐function mutations of the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic adenosine monophosphate (cAMP)‐regulated anion channel that mediates chloride/bicarbonate transport across epithelia (Gadsby et al , ; Cutting, ). CF is best known for its respiratory phenotype, yet also frequently leads to intestinal problems, as CFTR protein is strongly expressed all along the intestine (Gadsby et al , ; Ooi & Durie, ). CFTR is not only an anion channel, but also orchestrates proteostasis at respiratory and intestinal epithelial surfaces, meaning that it regulates adaptation to cell‐autonomous or environmental stress signals (Luciani et al , ; Villella et al , ,b; Ferrari et al , ).…”

Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings

“…The CFTR protein, which is essential in the regulation of chloride and sodium transport in epithelial cells [1], is highly expressed on the apical surface of intestinal epithelial cells, pancreatic ductal cells, and cholangiocytes in bile ducts which in the healthy transport ions, bicarbonate and fluid to the organs' lumen [2]. Thus, CFTR dysfunction results in viscous luminal secretions obstructing the bile and pancreatic ducts as well as the intestine [3].…”

“…Typical resulting GI symptoms are frequent and voluminous greasy stools, flatulence, abdominal bloating, constipation, abdominal pain, an impaired nutritional status, as well as failure to thrive. Even though GI symptoms are a hallmark of CF [5–7], often leading to diagnosis of the inherited disease, they are still insufficiently understood for why deeper investigations into the abdominal involvement in CF are needed [2]. Moreover, with enhanced survival due to improved therapeutic options and patient management, comorbidities of the GI, hepatobiliary, and pancreatic tract are of increasing clinical and scientific interest.…”