Dysmotility in the ileum of CFTR null swine

Abstract

Background: Gastrointestinal (GI) complications are a common source of morbidity for people with cystic fibrosis (pwCF). The pathobiology of these clinical presentations is not fully understood, but there is evidence that gut dysmotility may be a primary contributor.

Methods: We studied gut motility in ileum samples from CF (CFTR-/-) and wild-type (WT) swine at birth (P0) and one week of post-natal life (P7) using organ bath assays.

Results: Ileal samples from both WT and CF swine displayed spontaneous peristalsis. CF swine presented with reduced basal amplitude of the peristaltic waves compared to WT swine. Stimulating the ileal samples with increasing concentrations of acetylcholine (ACh) resulted in four main findings: 1) ACh increased the amplitude of smooth muscle contraction in all ileal samples in a dose-dependent manner. 2) At P7, ACh stimulation caused a significant increase in the maximum smooth muscle contraction in the WT but not in the CF samples. 3) Increasing doses of ACh caused fatigue-like contracting decline in smooth muscle from WT samples at both ages, but not in samples from CF swine. 4) ACh stimulation had no effect on the frequency of smooth muscle contraction in either genotype.

Conclusions: Our results show ileal dysmotility in the CF swine characterized by a decrease in basal peristalsis and weaker smooth muscle contraction. Our data suggest that GI dysmotility would impact chyme transit through the GI tract, which may predispose pwCF to intestinal manifestations associated with the disease.

Keywords: Cystic fibrosis; Gastrointestinal tract; Gut motility.