De Lisle RC, Roach E, Jansson K. Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol 293: G577-G584, 2007. First published July 5, 2007; doi:10.1152/ajpgi.00195.2007.-The accumulation of mucus in affected organs is characteristic of cystic fibrosis (CF). The CF mouse small intestine has dramatic mucus accumulation and exhibits slower interdigestive intestinal transit. These factors are proposed to play cooperative roles that foster small intestinal bacterial overgrowth (SIBO) and contribute to the innate immune response of the CF intestine. It was hypothesized that decreasing the mucus accumulation would reduce SIBO and might improve other aspects of the CF intestinal phenotype. To test this, solid chow-fed CF mice were treated with an osmotic laxative to improve gut hydration or liquid-fed mice were treated orally with N-acetylcysteine (NAC) to break mucin disulfide bonds. Treatment with laxative or NAC reduced mucus accumulation by 43% and 50%, respectively, as measured histologically as dilation of the intestinal crypts. Laxative and NAC also reduced bacterial overgrowth in the CF intestine by 92% and 63%, respectively. Treatment with laxative normalized small intestinal transit in CF mice, whereas NAC did not. The expression of innate immune response-related genes was significantly reduced in laxative-treated CF mice, whereas there was no significant effect in NACtreated CF mice. In summary, laxative and NAC treatments of CF mice reduced mucus accumulation to a similar extent, but laxative was more effective than NAC at reducing bacterial load. Eradication of bacterial overgrowth by laxative treatment was associated with normalized intestinal transit and a reduction in the innate immune response. These results suggest that both mucus accumulation and slowed interdigestive small intestinal transit contribute to SIBO in the CF intestine.small intestinal bacterial overgrowth MICE that lack the expression of the cystic fibrosis (CF) transmembrane conductance regulator (Cftr) gene have a severe intestinal phenotype with many of the problems that occur in human CF patients. These include the accumulation of mucus, intestinal obstruction, slowed small intestinal transit, small intestinal bacterial overgrowth (SIBO), inflammation, and failure to thrive (4 -6, 30). Of these changes, bacterial overgrowth is of interest because it can be responsible for the majority of the other aspects of the intestinal phenotype (22, 34).Secreted gel-forming mucins, mainly Muc2 in the intestine, bind bacteria and help carry them aborally for efficient clearance from the small intestine. When mucus clearance is impaired, bacteria can proliferate in the mucus and may use it as an energy source (36). Mucus accumulation in the CF intestine is in part due to the dehydrated, acidic environment as well as the altered glycosylation of mucins (38, 40), which may increase the viscosity of mucus. Our labora...