Bowel dysfunction in cystic fibrosis: Importance of breath testing

Lewindon, Peter; Robb, T. A.; Moore, D J; Davidson, Geoffrey P.; Martin, Andrew

doi:10.1046/j.1440-1754.1998.00159.x

Cited by 59 publications

(53 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Small intestine bacterial overgrowth has been found in 30 to 40% of CF patients by breath testing techniques (23,30), but the cause is unknown. The normal small intestine has low numbers of bacteria, and there are several mechanisms that play roles in minimizing microbial colonization (for a review, see reference 39).…”

Section: Discussionmentioning

confidence: 99%

“…Studies of the small intestine in humans with CF reported an increase in mononuclear cells in the duodenum (34) and increases in luminal albumin, immunoglobulins, eosinophil cationic protein, neutrophil elastase, interleukin-1␤, and interleukin-8, which suggest increased epithelial permeability and inflammation (40). The cause of intestinal inflammation in humans with CF is not known, but 30 to 40% of CF patients have been reported to have microbial overgrowth in the small intestine (23,30).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bacterial Overgrowth in the Cystic Fibrosis Transmembrane Conductance Regulator Null Mouse Small Intestine

2004

View full text Add to dashboard Cite

We recently reported the inflammation of the cystic fibrosis (CF) mouse small intestine, and we hypothesized bacterial overgrowth as a possible cause. Quantitative PCR of bacterial 16S genomic DNA in the CF mouse small intestine revealed an increase of greater than 40-fold compared to controls. Sequencing of 16S PCR products and Gram staining showed that the majority of bacteria in the CF mouse intestine were gram negative. Bacteria were observed to colonize the mucus that accumulates in the intestinal lumen of mice with CF. Impaired Paneth cell defenses were suggested by observation of partially dispersed Paneth granules in the mucus plugs of CF mouse intestinal crypts, and this mucus was strongly immunoreactive for Paneth cell bactericidal products. The role of bacterial overgrowth in intestinal inflammation in CF was tested by treating mice with oral antibiotics (ciprofloxacin and metronidazole) for 3 weeks, which reduced bacterial load in the CF mouse small intestine over 400-fold. Antibiotic treatment decreased the expression of the inflammationrelated genes mast cell protease 2, leucine-rich ␣2 glycoprotein/leucine-rich high endothelial venule glycoprotein, suppressor of cytokine signaling 3, hematopoietic cell transcript 1, and resistin-like molecule ␤/found in inflammatory zone 2, all of which were no longer expressed at levels significantly different from control levels. The reduction of intestinal bacteria also significantly improved the growth of CF mice but had no effect on the growth of wild-type mice. These data suggest that bacterial overgrowth in the CF mouse small intestine has a role in inflammation and contributes to the failure to thrive in this mouse model of CF.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bacterial Overgrowth in the Cystic Fibrosis Transmembrane Conductance Regulator Null Mouse Small Intestine

2004

View full text Add to dashboard Cite

show abstract

“…This suggests that secretion from goblet cells is stimulated by bacterial overgrowth. These results indicate that bacteria not only take advantage of mucus to colonize the small intestine but actively participate in stimulating mucus secretion by the intestinal epithelium.Another aspect of the CF intestinal phenotype related to bacterial overgrowth is that intestinal transit is impaired (1,13,19,27). The interdigestive intestinal motility (migrating motor complex) has a housekeeping function that "sweeps" the lumen clean and thereby removes mucus and embedded bacteria.…”

mentioning

confidence: 99%

“…Another aspect of the CF intestinal phenotype related to bacterial overgrowth is that intestinal transit is impaired (1,13,19,27). The interdigestive intestinal motility (migrating motor complex) has a housekeeping function that "sweeps" the lumen clean and thereby removes mucus and embedded bacteria.…”

mentioning

confidence: 99%

Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine

Lisle¹,

Roach²,

Jansson³

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

108

View full text Add to dashboard Cite

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...

show abstract

“…However, selected subgroups of both CF patients and HSs were assessed. 21 Van Biervliet et al assessed disaccharide activities and intestinal alkaline phosphatase (IAP) in small intestinal biopsy specimens of 61 newly diagnosed CF patients aged from 1 month to 14 years. Interestingly, in a significant number of patients (n¼19) Shmerling type II and III mucosa was stated.…”

Section: Discussionmentioning

confidence: 99%

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Mądry

Fidler

Sobczyńska-Tomaszewska

et al. 2011

Eur J Hum Genet

View full text Add to dashboard Cite

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with À13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (Po0.0028) and in patients with at least one mild mutation (Po0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.

show abstract

Bowel dysfunction in cystic fibrosis: Importance of breath testing

Abstract: Bacterial overgrowth and carbohydrate malabsorption, particularly of sucrose, should be considered when assessing children with CF and abnormal stool patterns.

Cited by 59 publications

References 0 publications

Bacterial Overgrowth in the Cystic Fibrosis Transmembrane Conductance Regulator Null Mouse Small Intestine

Bacterial Overgrowth in the Cystic Fibrosis Transmembrane Conductance Regulator Null Mouse Small Intestine

Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Contact Info

Product

Resources

About