The Enigmatic Gut in Cystic Fibrosis: Linking Inflammation, Dysbiosis, and the Increased Risk of Malignancy

Millie Garg, Chee Y. Ooi

Intestinal inflammation, dysbiosis, and increased gastrointestinal malignancy risks are well-described in patients with cystic fibrosis (CF). However, there is limited understanding of their pathophysiology. This review aims to discuss these issues and assess potential links between them. Evidence of links between intestinal inflammation and dysbiosis (an imbalance in intestinal microbial populations) exist. Recent studies have demonstrated reduction in intestinal inflammation with probiotic administration. Both bacterial dysbiosis and gut inflammation contribute to the suboptimal nutritional status seen in children with CF. Short-chain fatty acids may be reduced in the gut lumen as a result of bacterial imbalances and may promote inflammation. Inflammation and bacterial dysbiosis in CF may also contribute to emerging adult complications such as gastrointestinal malignancy. An increase in carcinogenic microbes and reduction in microbes protective against cancer have been found in CF, linking bacterial dysbiosis and cancer. Murine studies suggest the CF gene, cystic fibrosis transmembrane conductance regulator (CFTR) gene, itself may be a tumour suppressor gene. The pathophysiology of interactions among intestinal inflammation, dysbiosis, and malignancy in CF is not clearly understood and requires further research.