Small Intestinal Bacterial Overgrowth (SIBO Sample Clauses

Small Intestinal Bacterial Overgrowth (SIBO. (Breath Hydrogen Test) CFTR is expressed throughout the GI tract, with CFTR mRNA levels highest in the duodenum, including high expression in the pancreatic duct and mucus secreting Xxxxxxx'x glands.39, 40 Duodenal bicarbonate is secreted via a CFTR-assisted chloride-bicarbonate exchange process and an electrogenic secretion of bicarbonate via a CFTR conductance pathway.41 Bicarbonate is also essential to the functioning of naturally –occurring antimicrobials; decreased CFTR-mediated bicarbonate secretion may underlie dysbiosis. The defensins lysozyme and lactoferrin have decreased ability to kill bacteria at higher pH42. Our current understanding of the role of CFTR in the pathophysiology of dysbiosis in CF has been facilitated by studies using the CF mouse model. Analysis of bacterial 16S ribosomal genes has been used to classify the intraluminal bacteria of the wild type and CF mice. There was reduced species diversity in the CF intestine, with more than 90% of the microbes belonging to the Enterobacteriaceae family. Also, about 6% of the bacteria in CF mice were Clostridium perfringens, which was not detected in the wild type animals.43 A reduction in whole gut species diversity as measured by stool sampling is seen in humans with CF and distinguishes children with CF from those without CF.44, 45 A decrease in beneficial and abundance of potentially harmful species was found in F508del homozygotes and those classified with greater disease severity status with CF, suggesting a link among CFTR mutations and shifts in fecal microbiota.46 Small intestinal bacterial overgrowth (SIBO), is dysbiosis of the upper intestine. SIBO produces toxic byproducts and metabolites that can lead to enterocyte damage, malabsorption and malnutrition with diarrhea, abdominal distension, flatulence, steatorrhea, macrocytic anemia, and weight loss47 SIBO has been seen in up to 30-55% of patients with CF.48, 49 Although many factors can cause SIBO, defective bicarbonate secretion from CFTR dysfunction likely plays a central role in dysbiosis in the GI tract. Decreased dysbiosis would be expected with improvements in CFTR function and should be associated with improvements in nutritional and abdominal symptoms and signs in patients with CF. Breath testing can identify dysbiosis in the proximal GI tract. Breath testing will be performed in a subset of subjects enrolled in the Part B CORE study to evaluate if improvement in CFTR function can be demonstrated by examining the preval...
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