Colon Adenomas, Short Chain Fatty Acid Levels Predict Gut Microbiome Alterations in Cystic Fibrosis

Patients with cystic fibrosis (CF) appear to have significant alterations in their gut microenvironment, including impaired production of short chain fatty acids (SCFAs), indicating a correlation between the disease and reduced microbiome diversity, according to research presented at Digestive Disease Week 2021.

Alterations in the gut microbiome of patients with CF is largely attributed to thickened intestinal secretions, pancreatic exocrine insufficiency, and repetitive exposure to antibiotic medications. Researchers believe a perturbed gut microbiome may increase the risk of colon carcinogenesis, partly through impaired production of SCFAs.

This cross-sectional study included 21 patients with CF and 21 participants without CF who underwent screening or surveillance colonoscopy. At the time of colonoscopy, investigators collected colonic aspirate from each participant. The researchers performed a comprehensive SCFA profile and characterized the microbiome of each participant.

Additionally, the researchers performed standard alpha and beta diversity analyses and measured differentially abundant taxa. Analyses were then conducted to identify predictors of microbiome composition in patients with CF.

Patients with CF were younger and presented with a lower body mass index than those without CF. Additionally, participants with CF were more often white and non-Hispanic as well as never smokers. A significantly higher rate of adenomas was found in the group of patients with CF (67% vs 29%; P =.03).

Significant reductions were found in all branched SCFAs in patients with CF. These reduced SCFAs included 2-methylbutyrate, isobutyrate, isovalerate, hexanoate, and valerate.

Patients with CF also had significantly reduced microbiome alpha diversity (P =.01) and significant clustering by CF compared with controls (PERMANOVA P =.001). Those with CF had reductions in the relative abundance of several SCFA-producing bacteria.

The strongest independent predictors of microbiome composition in the group of patients with CF were levels of isovalerate and the presence of adenomas. Patients with CF who presented with adenomas also had reduced relative abundance of the SCFA producers Coproccocus spp. and Bacteroides caccae, as well as increased B. fragilis compared against patients with CF without adenomas.

Reference

Baldwin-Hunter BL, Rozenberg FD, Annavajhala MJ, et al. Alterations in gut microbiome in adults with cystic fibrosis associate with presence of colon adenomas and short chain fatty acid levels. Poster presented at: Digestive Disease Week Annual Meeting; May 21-23, 2021. Abstract Fr566.