Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis

Abstract

Cystic fibrosis gastrointestinal disease includes nutrient malabsorption and intestinal inflammation. We show that the abundances of Escherichia coli in fecal microbiota were significantly higher in young children with cystic fibrosis than in controls and correlated with fecal measures of nutrient malabsorption and inflammation, suggesting that E. coli could contribute to cystic fibrosis gastrointestinal dysfunction.

Keywords: Escherichia coli; cystic fibrosis; inflammation; malabsorption; microbiota.

Figure 1.

A, Box-and-whisker plot of the relative abundance of Escherichia coli in all fecal samples from young children in the study with and without cystic fibrosis (CF), revealing markedly higher abundance of E. coli in fecal samples from subjects with CF. Escherichia coli abundances in other non-CF populations from published and archived data are included for comparison, including 139 adult samples from the Human Microbiome Project (http://www.hmpdacc.org/) and 94 samples from a multinational microbiome study of healthy children and adults [7], partitioned into infants (aged ≤1 year), children (aged 1–3 years), and adults (aged >3 years). MetaPhlAn (see Methods) was used to analyze all samples. Similar results were obtained with 16S ribosomal RNA gene pyrosequencing (Spearman correlation = 0.896, P < .001). The relative E. coli abundances for the CF samples were significantly different from those obtained for all of the non-CF analyses shown (P < .01). B, Temporal pattern of E. coli abundance in fecal samples from children with (red) vs without (blue) CF. Relative abundance is plotted by age of source subject; 2 samples from a child older than 3 years and for which no there were comparison control samples are omitted for clarity. Subject numbers for children with CF are shown. The bold lines illustrate the average E. coli relative abundance for all CF (red) vs all non-CF (blue) samples within a year of age (ie, age 0 days to 365 days, 366 to 730 days, etc), with each average plotted at the midpoint for each year. Red asterisks indicate those samples from subjects with CF that were collected within 30 days after antibiotic treatment; 2 subjects with CF (113 and 114) never had any antibiotics recorded over their lifetimes. Abbreviations: CF, cystic fibrosis; HMP, Human Microbiome Project; MN, multinational.