Altered Stool Microbiota of Infants with Cystic Fibrosis Shows Reduction in Genera Associated with Immune Programming

Abstract

AbstractPrevious work from our group indicated a connection between the gastrointestinal microbiota of infants and children with cystic fibrosis (CF) and airway disease in this population. Here we examine the stool microbiota of infants with CF and from the general population who did not have CF over the first year of life. CF children had reduced gastrointestinal Bacteroides and Bifidobacterium beginning in infancy, even after adjusting for antibiotic treatment. We also identify several metabolic pathways that are enriched or under represented among the microbial communities in the stool of these young patients with CF as compared to children without CF. In vitro studies demonstrated that exposure of the apical face of a polarized Intestinal cell line to Bacteroides thetaiotaomicron significantly reduced production of IL-8 secreted from both the apical and basolateral face of these cells, suggesting a mechanism whereby changes in the intestinal microflora could impact systemic inflammation. This work further establishes a link between gastrointestinal microbiota, systemic inflammation and airway disease, and presents the opportunity for therapeutic probiotic interventions.Significance statementThere is a surprising link between gastrointestinal microbial communities and airway disease progression in CF. Here we show that infants with CF ≤1 year of age show a distinct stool microbiota compared with children of a comparable age from a general population cohort. We detect associations between stool microbes and airway exacerbation events in the cohort of infants with CF, and in vitro studies provide a possible mechanism for this observation. These data argue that current therapeutics do not establish a healthy-like gastrointestinal microbiota in young patients with CF, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide benefit to these patients.