Highlights
- •Adults with CF had reductions in short chain fatty acid (SCFA)-producing bacteria.
- •CF patients had reduced levels of branched chain fatty acids but not of SCFAs.
- •CF patients with adenomas had increased Bacteroides fragilis.
Abstract
Background
Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients
have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs),
although it is unclear whether this corresponds with intestinal SCFA levels and the
presence of colonic neoplasia. The aim of this study was to compare gut microbiome
and SCFA composition in patients with and without CF, and to assess associations with
colonic adenomas.
Methods
Colonic aspirates were obtained from adults with and without CF undergoing colon cancer
screening or surveillance colonoscopy. Microbiome characterization was performed by
16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was
performed by LC-MS.
Results
42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced
alpha diversity and decreased relative abundance of many SCFA-producing taxa. There
were no significant differences in SCFA levels in CF patients, although there were
reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients
with adenomas, but not controls with adenomas, had significantly increased relative
abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration
and the presence of adenomas.
Conclusions
CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas
had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were
found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.
Keywords
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Article info
Publication history
Published online: January 28, 2023
Accepted:
January 23,
2023
Received in revised form:
December 2,
2022
Received:
August 5,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
