A systematic review of the colorectal microbiome in adult cystic fibrosis patients.

Abstract

Cystic fibrosis (CF) is a hereditary, life-limiting, multi-system condition that results in chronic respiratory infections, pancreatic insufficiency and intestinal inflammation. Evidence indicates that CF patients develop colorectal cancer (CRC) earlier and more often than the general population. Intestinal dysbiosis resulting from genetics and CF treatment is a contributing factor. This systematic review aims to evaluate the literature to compare the microbiome of adult CF patients to non-CF patients and to assess if these changes correspond with known CRC microbiome alterations. A systematic review across five databases was performed according to PRISMA guidelines. Studies focusing on adult CF patients using next generation sequencing and with appropriate non-CF controls were included. Two reviewers independently screened results and assessed study quality using the Newcastle-Ottawa scale. The search generated 2757 results. 118 studies were retained after reviewing the title/abstract and full article review found five studies met the inclusion criteria. All studies consistently showed reduced microbial diversity in CF patients and unique clustering between CF and control cohorts. Thirty-four genera and 27 species were differently expressed between CF and controls. The CF cohort had a reduced number of short-chain fatty acid (SCFA) producing bacteria and a higher abundance of bacteria associated with CRC compared to controls. There was substantial heterogeneity across all the studies with regard to methodologies and reporting. However, all studies consistently found CF patients had reduced microbial diversity, fewer SCFA producing bacteria and increased CRC-associated bacteria. Further prospective studies employing consistent multi-omics approaches are needed to improve our understanding of the CF gut microbiome and its involvement in early onset CRC. This is the first systematic review to assess adult CF colorectal microbiome changes. This study shows CF patients have reduced SCFA producing bacteria and increased CRC-associated bacteria compared to non-CF patients and may help to explain the increased risk of CRC in the CF cohort.