This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Small intestinal motility protects against bacterial overgrowth and is important for proper nutrition. Cystic fibrosis (CF) is one of the most common lethal genetic diseases and about half of CF patients have dysfunction of gastrointestinal motility and small intestinal bacterial overgrowth. Childhood failure-to-thrive and life-long nutritional problems are common in CF. Rationale: Poor nutrition is strongly correlated with the progression to airway failure and death in CF. At what age intestinal dysmotility develops in CF, and by what mechanisms, are not known. The long term goal is to understand intestinal dysfunction in CF in order to provide new therapeutic directions to improve health. Questions: The goal is to determine the relationships between bacterial overgrowth, inflammation, and intestinal muscle dysfunction during postnatal development. Design: The CF mouse model exhibits similar intestinal problems as human CF patients and will be used as an experimental model for this project. The objectives in this application are to determine the temporal relationships between altered metabolism of prostaglandins, intestinal muscle dysfunction, and bacterial overgrowth during development of the CF mouse small intestine. Outcomes: (1) Determine when prostaglandin metabolism is altered, by measuring expression of prostaglandin metabolic enzymes and levels of prostaglandins;(2) Determine when circular muscle activity is impaired, by measuring muscle behavior;and (3) Determine when abnormal bacterial growth occurs. The developmental time courses of these changes will be revealing about the causes of intestinal dysfunction in CF.
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