title: Metagenomic evidence for taxonomic dysbiosis and functional imbalance in the gastrointestinal tracts of children with cystic fibrosis.
abstract: Cystic fibrosis (CF) results in inflammation, malabsorption of fats and other nutrients, and obstruction in the gastrointestinal (GI) tract, yet the mechanisms linking these disease manifestations to microbiome composition remain largely unexplored. Here we used metagenomic analysis to systematically characterize fecal microbiomes of children with and without CF, demonstrating marked CF-associated taxonomic dysbiosis and functional imbalance. We further showed that these taxonomic and functional shifts were especially pronounced in young children with CF and diminished with age. Importantly, the resulting dysbiotic microbiomes had significantly altered capacities for lipid metabolism, including decreased capacity for overall fatty acid biosynthesis and increased capacity for degrading anti-inflammatory short-chain fatty acids. Notably, these functional differences correlated with fecal measures of fat malabsorption and inflammation. Combined, these results suggest that enteric fat abundance selects for pro-inflammatory GI microbiota in young children with CF, offering novel strategies for improving the health of children with CF-associated fat malabsorption.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, US.
authors.forename: Ohad
authors.initials: O
authors.lastname: Manor
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, US.
authors.forename: Roie
authors.initials: R
authors.lastname: Levy
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, US.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pope
authors.affiliation: Department of Microbiology, University of Washington, Seattle, US.
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.affiliation: Department of Microbiology, University of Washington, Seattle, US.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Brittnacher
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, US.
authors.forename: Rogan
authors.initials: R
authors.lastname: Carr
authors.affiliation: Department of Microbiology, University of Washington, Seattle, US.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Radey
authors.affiliation: Department of Microbiology, University of Washington, Seattle, US.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Hager
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, US.|Seattle Children's Hospital, Washington, US.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, US.|Seattle Children's Hospital, Washington, US.
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, US.|Department of Microbiology, University of Washington, Seattle, US.|Department of Medicine, University of Washington, Seattle, US.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, US.|Department of Microbiology, University of Washington, Seattle, US.|Seattle Children's Hospital, Washington, US.
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Hoffman
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, US.|Department of Computer Science and Engineering, University of Washington, Seattle, US.|Santa Fe Institute, New Mexico, US.
authors.forename: Elhanan
authors.initials: E
authors.lastname: Borenstein
mesh_terms: D039903:Actinobacteria / Q000235:genetics*; D044822:Biodiversity; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology*; D058893:DNA Barcoding, Taxonomic; D064806:Dysbiosis / Q000235:genetics / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D054892:Metagenome; D020560:Proteobacteria / Q000235:genetics*
chemical_list: D039841:Leukocyte L1 Antigen Complex