title: Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.
abstract: BACKGROUND
  In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age.
  
  
  METHODS
  Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure.
  
  
  RESULTS
  Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced.
  
  
  CONCLUSIONS
  This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.
authors.affiliation: Public Health and Infectious Diseases Department, Microbiology Unit, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Schippa
authors.forename: Valerio
authors.initials: V
authors.lastname: Iebba
authors.forename: Floriana
authors.initials: F
authors.lastname: Santangelo
authors.forename: Antonella
authors.initials: A
authors.lastname: Gagliardi
authors.forename: Riccardo Valerio
authors.initials: RV
authors.lastname: De Biase
authors.forename: Antonella
authors.initials: A
authors.lastname: Stamato
authors.forename: Serenella
authors.initials: S
authors.lastname: Bertasi
authors.forename: Marco
authors.initials: M
authors.lastname: Lucarelli
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Conte
authors.forename: Serena
authors.initials: S
authors.lastname: Quattrucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics* / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003710:Demography; D016002:Discriminant Analysis; D004587:Electrophoresis, Agar Gel; D005243:Feces / Q000382:microbiology*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012720:Severity of Illness Index; D013045:Species Specificity; D055815:Young Adult
chemical_list: D012336:RNA, Ribosomal, 16S; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator