Mucus accumulation, luminal acidification, and intestinal blockages caused by dysmotility alter the mucosa-attached microbiome and epithelial cells and contribute to the development of gastrointestinal diseases in patients with cystic fibrosis (CF), according to a new study published in Scientific Reports.
Researchers obtained 28 ileal biopsies from 7 individuals without CF who underwent investigative endoscopies and compared them to ileal tissue from 1 individual diagnosed with CF. Additionally, the investigators compared the intestinal microbiome and epithelial cell profiles of wild-type mice with cystic fibrosis transmembrane conductance regulator (CFTR)-knockout mice and F508del-mutant mice with CF.
The researchers analyzed the microbial diversity of both humans and mice using Illumina 16S rRNA gene sequencing. They noted an almost tenfold decrease in microbial diversity in the patient with CF whose ileum exhibited 25 variants compared with an average of 239 variants in the ilea of the 7 individuals without CF.
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Similarly, the wild-type mice demonstrated significantly more microbial diversity than the CFTR-knockout mice (P <.05), and the CFTR-knockout mice exhibited reduced microbial diversity along the length of the small intestine (P <.01). The increased presence of inflammatory-causing Escherichia and decreased bile-acid-producing bacteria differentiated the mucosa-attached microbiome of the mice with CF compared to the wild-type mice.
Compared with the wild-type mice, F508del-mutant mice exhibited increased microbes in the Peptostreptococcaceae and Lachnospiraceae families, and multiple strains of Enterobacteriaceae-classified amplicon sequence variants including Shigella and Escherichia species. Increased Bifidobacterium strains were present within fecal samples obtained from the mice and the patient with CF.
The researchers used immunohistochemistry to profile ileal epithelial cells. Both the ilea of the mice and the individual with CF contained increased stem and secretory goblet cells and decreased absorptive enterocytes, secretory Paneth cells, and L-type enteroendocrine cells which secrete glucagon-like peptides 1 and 2.
“The abnormal environment of the intestinal lumen in CF promotes microbial dysbiosis, deregulating the proliferation and differentiation of intestinal epithelial cells,” the authors said. “These changes in the mucosa-attached microbiome and epithelial cell profile suggest that microbiota-host interactions may contribute to intestinal CF disease development with implications for therapy.”
Kelly J, Al-Rammahi M, Daly K, et al. Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease. Sci Rep. 2022;12(1):6593. doi:10.1038/s41598-022-10328-3