Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease



Kelly, Jennifer, Al-Rammahi, Miran ORCID: 0000-0002-0165-7990, Daly, Kristian ORCID: 0000-0002-1075-1831, Flanagan, Paul K, Urs, Arun, Cohen, Marta C, di Stefano, Gabriella, Bijvelds, Marcel JC, Sheppard, David N, de Jonge, Hugo R
et al (show 2 more authors) (2022) Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease. SCIENTIFIC REPORTS, 12 (1). 6593-.

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Abstract

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Defective CFTR leads to accumulation of dehydrated viscous mucus within the small intestine, luminal acidification and altered intestinal motility, resulting in blockage. These changes promote gut microbial dysbiosis, adversely influencing the normal proliferation and differentiation of intestinal epithelial cells. Using Illumina 16S rRNA gene sequencing and immunohistochemistry, we assessed changes in mucosa-attached microbiome and epithelial cell profile in the small intestine of CF mice and a CF patient compared to wild-type mice and non-CF humans. We found increased abundance of pro-inflammatory Escherichia and depletion of beneficial secondary bile-acid producing bacteria in the ileal mucosa-attached microbiome of CFTR-null mice. The ileal mucosa in a CF patient was dominated by a non-aeruginosa Pseudomonas species and lacked numerous beneficial anti-inflammatory and short-chain fatty acid-producing bacteria. In the ileum of both CF mice and a CF patient, the number of absorptive enterocytes, Paneth and glucagon-like peptide 1 and 2 secreting L-type enteroendocrine cells were decreased, whereas stem and goblet cell numbers were increased. These changes in mucosa-attached microbiome and epithelial cell profile suggest that microbiota-host interactions may contribute to intestinal CF disease development with implications for therapy.

Item Type: Article
Uncontrolled Keywords: Intestinal Mucosa, Goblet Cells, Intestine, Small, Animals, Humans, Mice, Bacteria, Intestinal Diseases, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, RNA, Ribosomal, 16S, Cell Count, Microbiota
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 12 Apr 2022 14:59
Last Modified: 18 Jan 2023 21:05
DOI: 10.1038/s41598-022-10328-3
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3152799