title: Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study.
abstract: BACKGROUND
  Although scientific knowledge about the benefits of probiotic use in cystis fibrosis (CF) is scarce, their expectative is promising. The aim of this work was to analyze the effect of a Lactobacillus reuteri probiotic preparation versus placebo in CF patients.
  
  
  METHODS
  A prospective, double blind, crossover and with placebo study was carried out in 30 CF patients from two Spanish hospitals. Patients were randomized in Group A (6 months of probiotic followed by 6 months of placebo) and Group B (6 months of placebo followed by 6 months of probiotic). GIQLI (gastrointestinal) and SF-12 (general) health tests were performed after probiotic and placebo intakes. Fat absorption coefficient, calprotectin, and inflammatory interleukin quantification were determined in fecal samples. Total fecal DNA was obtained and metagenomic 454-pyrosequencing was applied to analyze the microbiome composition. STATA v12 MP software was used for statistical analyses.
  
  
  RESULTS
  Statistically significant improvement in the gastrointestinal health and decrease of the calprotectin levels were demonstrated in patients after probiotic exposure, in comparison with placebo. All CF subjects reported good tolerance to L. reuteri without secondary effects. Metagenomic analysis showed an important dysbiosis in CF gut microbiota associated with a high concentration of Proteobacteria. Probiotic intake was followed by a reduction in the total bacterial density, mostly due to a considerable reduction in the γ-Proteobacteria phylum; and an important increase of the microbial diversity with a higher representation of Firmicutes.
  
  
  CONCLUSIONS
  Probiotics might ameliorate the dysbiosis of CF gut microbiota, characterized by a high density of Proteobacterial organisms. L. reuteri significantly decrease intestinal inflammation and increase digestive comfort.
authors.affiliation: Department of Microbiology, Hospital Universitario Ramón y Cajal, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Spanish Network for the Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Spain. Electronic address: rosacampo@yahoo.com.
authors.forename: Rosa
authors.initials: R
authors.lastname: del Campo
authors.affiliation: Cystic Fibrosis Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Garriga
authors.affiliation: Department of Pediatrics, Virgen de las Nieves and San Cecilio University Hospitals, Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez-Aragón
authors.affiliation: Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Guallarte
authors.affiliation: Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Cystic Fibrosis Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Adelaida
authors.initials: A
authors.lastname: Lamas
authors.affiliation: Cystic Fibrosis Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Máiz
authors.affiliation: Deparment of Biochemistry, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Bayón
authors.affiliation: Department of Immunology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Garbiñe
authors.initials: G
authors.lastname: Roy
authors.affiliation: Department of Microbiology, Hospital Universitario Ramón y Cajal, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Spanish Network for the Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cantón
authors.affiliation: Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain; Center for Network Research in Epidemiology and Public Health (CIBERESP), Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Zamora
authors.affiliation: Department of Microbiology, Hospital Universitario Ramón y Cajal, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Center for Network Research in Epidemiology and Public Health (CIBERESP), Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Baquero
authors.affiliation: Cystic Fibrosis Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Suárez
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology*; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D052200:Limosilactobacillus reuteri; D008297:Male; D056186:Metagenomics; D064307:Microbiota; D019936:Probiotics / Q000627:therapeutic use*; D011446:Prospective Studies; D020560:Proteobacteria / Q000302:isolation & purification; D055815:Young Adult
keywords: Digestive health; Intestinal microbiota; Lactobacillus reuteri; Probiotics