title: Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial.
abstract: OBJECTIVE
  Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment.
  
  
  METHODS
  The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG.
  
  
  RESULTS
  Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2-9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2 (-), respectively; P<0.01). Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation.
  
  
  CONCLUSIONS
  CF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota, supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT 01961661.
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bruzzese
authors.affiliation: Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Callegari
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Raia
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Viscovo
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Scotto
authors.affiliation: Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Morelli
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Buccigrossi
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lo Vecchio
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Ruberto
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University Federico II, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guarino
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology*; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D007778:Lactobacillus / Q000502:physiology*; D008297:Male; D064307:Microbiota / Q000235:genetics; D019936:Probiotics / Q000494:pharmacology