title: Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis.
abstract: OBJECTIVE
  Cirrhosis (CIR) occurs in 5-7% of cystic fibrosis (CF) patients. We hypothesized that alterations in intestinal function in CF contribute to the development of CIR.
  
  
  OBJECTIVE
  Determine the frequency of macroscopic intestinal lesions, intestinal inflammation, intestinal permeability and characterize fecal microbiome in CF CIR subjects and CF subjects with no liver disease (CFnoLIV).
  
  
  METHODS
  11 subjects with CFCIR (6 M, 12.8 yrs ± 3.8) and 19 matched with CFnoLIV (10 M, 12.6 yrs ± 3.4) underwent small bowel capsule endoscopy, intestinal permeability testing by urinary lactulose: mannitol excretion ratio, fecal calprotectin determination and fecal microbiome characterization.
  
  
  RESULTS
  CFCIR and CFnoLIV did not differ in key demographics or CF complications. CFCIR had higher GGT (59±51 U/L vs 17±4 p = 0.02) and lower platelet count (187±126 vs 283±60 p = 0.04) and weight (-0.86 ± 1.0 vs 0.30 ± 0.9 p = 0.002) z scores. CFCIR had more severe intestinal mucosal lesions on capsule endoscopy (score ≥4, 4/11 vs 0/19 p = 0.01). Fecal calprotectin was similar between CFCIR and CFnoLIV (166 μg/g ±175 vs 136 ± 193 p = 0.58, nl <120). Lactulose:mannitol ratio was elevated in 27/28 subjects and was slightly lower in CFCIR vs CFnoLIV (0.08±0.02 vs 0.11±0.05, p = 0.04, nl ≤0.03). Small bowel transit time was longer in CFCIR vs CFnoLIV (195±42 min vs 167±68 p<0.001, nl 274 ± 41). Bacteroides were decreased in relative abundance in CFCIR and were associated with lower capsule endoscopy score whereas Clostridium were more abundant in CFCIR and associated with higher capsule endoscopy score.
  
  
  CONCLUSIONS
  CFCIR is associated with increased intestinal mucosal lesions, slower small bowel transit time and alterations in fecal microbiome. Abnormal intestinal permeability and elevated fecal calprotectin are common in all CF subjects. Disturbances in intestinal function in CF combined with changes in the microbiome may contribute to the development of hepatic fibrosis and intestinal lesions.
authors: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America.
authors: Thomas
authors: T
authors: Flass
authors: Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital, Aurora, Colorado, United States of America.
authors: Suhong
authors: S
authors: Tong
authors: Department of Infectious Diseases, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: Daniel N
authors: DN
authors: Frank
authors: Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital, Aurora, Colorado, United States of America; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, United States of America.
authors: Brandie D
authors: BD
authors: Wagner
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, United States of America.
authors: Charles E
authors: CE
authors: Robertson
authors: Department of Infectious Diseases, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: Cassandra Vogel
authors: CV
authors: Kotter
authors: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America; Colorado Clinical and Translational Sciences Institute, University of Colorado School of Medicine, Aurora, CO, United States of America.
authors: Ronald J
authors: RJ
authors: Sokol
authors: Section of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America.
authors: Edith
authors: E
authors: Zemanick
authors: Section of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America.
authors: Frank
authors: F
authors: Accurso
authors: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America.
authors: Edward J
authors: EJ
authors: Hoffenberg
authors: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, United States of America.
authors: Michael R
authors: MR
authors: Narkewicz
mesh_terms: D000293:Adolescent; D053705:Capsule Endoscopes; D016022:Case-Control Studies; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology / Q000473:pathology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008103:Liver Cirrhosis / Q000382:microbiology; D008297:Male; D010539:Permeability
chemical_list: D039841:Leukocyte L1 Antigen Complex