Cystic fibrosis mouse model-dependent intestinal structure and gut microbiome

• Published in: Mammalian genome Vol. 26; no. 5-6; pp. 222 - 234
• Main Authors: Bazett, Mark, Honeyman, Lisa, Stefanov, Anguel N., Pope, Christopher E., Hoffman, Lucas R., Haston, Christina K.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2015; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Animals; Bacterial Load; Bifidobacterium; Biomedical and Life Sciences; Body Weight; Cell Biology; Cystic Fibrosis - genetics; Cystic Fibrosis - microbiology; Cystic Fibrosis - pathology; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Disease Models, Animal; DNA, Bacterial - genetics; Gastrointestinal Microbiome; Human Genetics; Intestines - microbiology; Intestines - pathology; Lactobacillus; Life Sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phenotype; RNA, Ribosomal, 16S - genetics; Bacterial Load; Cystic Fibrosis; Goblet Cell Hyperplasia; Muscle Thickness; Small Intestinal Bacterial Overgrowth
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s00335-015-9560-4

Mice with a null mutation in the cystic fibrosis transmembrane conductance regulator ( Cftr ) gene show intestinal structure alterations and bacterial overgrowth. To determine whether these changes are model-dependent and whether the intestinal microbiome is altered in cystic fibrosis (CF) mouse models, we characterized the ileal tissue and intestinal microbiome of mice with the clinically common ΔF508 Cftr mutation (FVB/N Cftr tm1Eur ) and with Cftr null mutations (BALB/c Cftr tm1UNC and C57BL/6 Cftr tm1UNC ). Intestinal disease in 12-week-old CF mice, relative to wild-type strain controls, was measured histologically. The microbiome was characterized by pyrosequencing of the V4–V6 region of the 16S rRNA gene and intestinal load was measured by RT-PCR of the 16S rRNA gene. The CF-associated increases in ileal crypt to villus axis distention, goblet cell hyperplasia, and muscularis externa thickness were more severe in the BALB/c and C57BL/6 Cftr tm1UNC mice than in the FVB/N Cftr tm1Eur mice. Intestinal bacterial load was significantly increased in all CF models, compared to levels in controls, and positively correlated with circular muscle thickness in CF, but not wild-type, mice. Microbiome profiling identified Bifidobacterium and groups of Lactobacillus to be of altered abundance in the CF mice but overall bacterial frequencies were not common to the three CF strains and were not correlative of major histological changes. In conclusion, intestinal structure alterations, bacterial overgrowth, and dysbiosis were each more severe in BALB/c and C57BL/6 Cftr tm1UNC mice than in the FVB/N Cftr tm1Eur mice. The intestinal microbiome differed among the three CF mouse models.