Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

Marsh, Ryan; Gavillet, Helen; Hanson, Liam; Ng, Christabella; Mitchell-Whyte, Mandisa; Major, Giles; Smyth, Alan R; Rivett, Damian; van der Gast, Christopher

Abstract

Background Most people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health.

Study Design Faecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships.

Results pwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed.

Conclusions Alterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.

Citation

Marsh, R., Gavillet, H., Hanson, L., Ng, C., Mitchell-Whyte, M., Major, G., …van der Gast, C. Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

• Working Paper Type: Working Paper
• Deposit Date: Jan 30, 2022
• Publicly Available Date: Jan 31, 2022
• Public URL: https://nottingham-repository.worktribe.com/output/7356717
• Publisher URL: https://www.medrxiv.org/content/10.1101/2021.08.24.21262265v2
• Additional Information: Preprint posted in medRXiv August 28, 2021. Now published in Journal of Cystic Fibrosis doi: 10.1016/j.jcf.2021.11.014