Metagenomic evidence for taxonomic dysbiosis and functional imbalance in the gastrointestinal tracts of children with cystic fibrosis

• DOI: 10.1038/srep22493
• Publication Date: 2016-03-04T10:14:52Z
• Authors: Ohad Manor; Roie Levy; Christopher E. Pope; Hillary S. Hayden; Mitchell J. Britt...; Rogan Carr; Matthew C. Radey; Kyle R. Hager; Sonya L. Heltshe; Bonnie W. Ramsey; Samuel I. Miller; Lucas R. Hoffman; Elhanan Borenstein
• Keywords: 0303 health sciences; Cystic Fibrosis; Infant, Newborn; Infant; Biodiversity; Article; Gastrointestinal Microbiome; 3. Good health; Actinobacteria; Gastrointestinal Tract; Feces; 03 medical and health sciences; Child, Preschool; Proteobacteria; DNA Barcoding, Taxonomic; Dysbiosis; Humans; Metagenome; Leukocyte L1 Antigen Complex

AbstractCystic 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.