Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype

• DOI: 10.1371/journal.pone.0208171
• Publication Date: 2018-12-06T21:26:19Z
• Authors: Pamela Vernocchi; Federica Del Chie...; Alessandra Russo; Fabio Majo; Martina Rossitto; Mariacristina Val...; Luca Casadei; Antonietta La Storia; Francesca De Fili...; Cristiano Rizzo; Cesare Manetti; Paola Paci; Danilo Ercolini; Federico Marini; Ersilia Vita Fisc...; Bruno Dallapiccola; Vincenzina Lucidi; Alfredo Miccheli; Lorenza Putignani
• Keywords: Genetics and Molecular Biology (all); Male; 0301 basic medicine; Cystic Fibrosis; Science; Cystic Fibrosis Transmembrane Conductance Regulator; Biochemistry; Cohort Studies; Feces; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); Humans; Metabolomics; Intestinal Mucosa; Bacteria; Host Microbial Interactions; Q; R; COMPUTATIONAL AND SYSTEMS BIOLOGY; Anti-Bacterial Agents; Gastrointestinal Microbiome; 3. Good health; Phenotype; Agricultural and Biological Sciences (all); Child, Preschool; anti-bacterialaAgents; bacteria; child, preschool; Cohort studies; cystic fibrosis; cystic fibrosis transmembrane conductance regulator; dysbiosis; exocrine pancreatic insufficiency; feces; female; gastrointestinal microbiome; host microbial Interactions; humans; intestinal mucosa; male; Metabolomics; metagenomics; phenotype; Medicine; Dysbiosis; Exocrine Pancreatic Insufficiency; Female; Metagenomics; Research Article

Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.