17 research outputs found
Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis.
BACKGROUND AND AIMS: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. AIMS: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
Associations of gut microbiome and clinical parameters.
<p>Associations between bacterial phyla (panel A) and lower-level taxa (e.g., genera, families; panel B) and selected clinical parameters are color-coded in the heatmaps by magnitude of Spearman’s correlation coefficient. The boxplots in panel A display the variation in relative abundances of Firmicutes and Bacteroidetes as a function of the number of intestinal red spots visualized by capsule endoscopy. Asterisks denote p-values < = 0.05 resulting from Spearman rank correlation tests.</p
Video Capsule Endoscopy Scores.
<p>Scores derived from the scoring system of Maiden et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116967#pone.0116967.ref032" target="_blank">32</a>], where 1 point is assigned for each individual presence of each finding (except blood).</p><p>CFnoLIV: CF subjects with no evidence of liver disease (normal exam and ALT), CFCIR: CF subjects with cirrhosis.</p><p>Video Capsule Endoscopy Scores.</p
Video capsule endoscopy results.
<p>Representative findings from a normal video capsule endoscopy image (A) and an abnormal video capsule endoscopy demonstrating a red spot (B).</p
Boxplots of selected phyla and genera associated with clinical parameters.
<p>Boxplots of selected phyla and genera associated with clinical parameters.</p
Measures of intestinal permeability and inflammation.
<p>Scatterplot comparing lactulose/mannitol urinary excretion ratio to fecal calprotectin by CFCIR (circles) or CFnoLIV (squares) stratified by significant video capsule findings (score of ≥4: solid circles) compared to mild or no findings (score of ≤3: open circles or squares). There were no CFnoLIV with a score of ≥4.</p
Results of multivariate analysis of fecal microbiomes for single predictor variables.
<p><sup>1</sup>Determined by permutation-based multivariate analysis of variance test of OTU count data (adonis function of vegan R package). [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116967#pone.0116967.ref060" target="_blank">60</a>] Separate analyses were performed for OTU data organized at genus-, and phylum-level. P-values less than 0.1 are highlighted in bold.</p><p>CFCIR = CF with cirrhosis, CFnoLiv = CF with no evidence of liver disease.</p><p>Results of multivariate analysis of fecal microbiomes for single predictor variables.</p