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Altered transit and bacterial overgrowth in the cystic fibrosis mouse small intestine
1Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA. rdelisle@kumc.edu
Abstract:
Small intestinal bacterial overgrowth (SIBO) may play an important role in the gastrointestinal complications of cystic fibrosis (CF). This work explored two potential factors in development of SIBO in the CF (cftr(tm1UNC)) mouse: impaired Paneth cell innate defenses and altered gastrointestinal motility. Postnatal differentiation of Paneth cells was followed by Defcr, Lyzs, and Ang4 gene expression, and SIBO was measured by quantitative PCR of the bacterial 16S rRNA gene. Paneth cell gene expression was low in 4-day-old CF and wild-type (WT) mice and increased similarly in both groups of mice between 12 and 16 days. Peak Paneth cell gene expression was reached by 40 days of age and was less for Defcr and Lyzs in CF mice compared with WT, whereas Ang4 levels were greater in CF mice. SIBO occurred by postnatal day 8 in CF mice, which is before Paneth cell development. With the use of gavaged rhodamine-dextran to follow motility, gastric emptying in CF mice was slightly decreased compared with WT, and small intestinal transit was dramatically less. Since antibiotics improve weight gain in CF mice, their effects on gastric emptying and small intestinal transit were determined. Antibiotics did not affect gastric emptying or transit in CF mice but did significantly slow intestinal transit in WT mice, suggesting a potential role of normal microflora in regulating transit. In conclusion, small intestinal transit was significantly slower in CF mice, and this is likely a major factor in SIBO in CF.
Insights
Small intestinal bacterial overgrowth (SIBO) in cystic fibrosis (CF) mice is linked to significantly slower intestinal transit, not impaired Paneth cell defenses. This finding highlights motility as a key factor in CF gastrointestinal issues.
Area of Science:
- Gastroenterology
- Microbiology
- Genetics
Background:
- Small intestinal bacterial overgrowth (SIBO) is a potential complication in cystic fibrosis (CF).
- Paneth cell dysfunction and altered gastrointestinal motility are investigated as contributing factors to SIBO in CF.
Purpose of the Study:
- To explore the roles of impaired Paneth cell innate defenses and altered gastrointestinal motility in the development of SIBO in CF mice.
- To determine the relationship between Paneth cell gene expression, gastrointestinal transit, and SIBO in CF.
Main Methods:
- Quantitative PCR was used to measure bacterial 16S rRNA gene for SIBO and Paneth cell gene expression (Defcr, Lyzs, Ang4).
- Gastric emptying and small intestinal transit were assessed using rhodamine-dextran in CF and wild-type (WT) mice.
- The effects of antibiotics on gastrointestinal transit were evaluated in both CF and WT mice.
Main Results:
- Paneth cell gene expression showed differences between CF and WT mice by 40 days of age, with lower Defcr and Lyzs, and higher Ang4 in CF mice.
- SIBO was detected in CF mice by postnatal day 8, preceding full Paneth cell development.
- CF mice exhibited significantly slower small intestinal transit compared to WT mice.
- Antibiotics did not alter transit in CF mice but slowed it in WT mice, suggesting a role for normal microflora.
Conclusions:
- Significantly slowed small intestinal transit in CF mice is identified as a likely major factor contributing to SIBO.
- Impaired Paneth cell defenses may play a lesser role in SIBO development in CF compared to motility issues.
- Altered gastrointestinal motility is a critical consideration for managing SIBO in cystic fibrosis.
