Moana Mika1, Insa Korten2, Weihong Qi3, Nicolas Regamey4, Urs Frey5, Carmen Casaulta6, Philipp Latzin7, Markus Hilty8. 1. Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. 2. Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland; University Children's Hospital (UKBB), Basel, Switzerland. 3. Functional Genomics Center, Swiss Federal Institute of Technology Zurich, University of Zurich, Zurich, Switzerland. 4. Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland; Children's Hospital, Lucerne, Switzerland. 5. University Children's Hospital (UKBB), Basel, Switzerland. 6. Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland. 7. Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland; University Children's Hospital (UKBB), Basel, Switzerland. 8. Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: markus.hilty@ifik.unibe.ch.
Abstract
BACKGROUND: Respiratory tract infections and subsequent airway inflammation occur early in the life of infants with cystic fibrosis. However, detailed information about the microbial composition of the respiratory tract in infants with this disorder is scarce. We aimed to undertake longitudinal in-depth characterisation of the upper respiratory tract microbiota in infants with cystic fibrosis during the first year of life. METHODS: We did this prospective cohort study at seven cystic fibrosis centres in Switzerland. Between Feb 1, 2011, and May 31, 2014, we enrolled 30 infants with a diagnosis of cystic fibrosis. Microbiota characterisation was done with 16S rRNA gene pyrosequencing and oligotyping of nasal swabs collected every 2 weeks from the infants with cystic fibrosis. We compared these data with data for an age-matched cohort of 47 healthy infants. We additionally investigated the effect of antibiotic treatment on the microbiota of infants with cystic fibrosis. Statistical methods included regression analyses with a multivariable multilevel linear model with random effects to correct for clustering on the individual level. FINDINGS: We analysed 461 nasal swabs taken from the infants with cystic fibrosis; the cohort of healthy infants comprised 872 samples. The microbiota of infants with cystic fibrosis differed compositionally from that of healthy infants (p=0·001). This difference was also found in exclusively antibiotic-naive samples (p=0·001). The disordering was mainly, but not solely, due to an overall increase in the mean relative abundance of Staphylococcaceae in infants with cystic fibrosis compared with healthy infants (multivariable linear regression model stratified by age and adjusted for season; second month: coefficient 16·2 [95% CI 0·6-31·9]; p=0·04; third month: 17·9 [3·3-32·5]; p=0·02; fourth month: 21·1 [7·8-34·3]; p=0·002). Oligotyping analysis enabled differentiation between Staphylococcus aureus and coagulase-negative Staphylococci. Whereas the analysis showed a decrease in S aureus at and after antibiotic treatment, coagulase-negative Staphylococci increased. INTERPRETATION: Our study describes compositional differences in the microbiota of infants with cystic fibrosis compared with healthy controls, and disordering of the microbiota on antibiotic administration. Besides S aureus, coagulase-negative Staphylococci also contributed to the disordering identified in these infants. These findings are clinically important in view of the crucial role that bacterial pathogens have in the disease progression of cystic fibrosis in early life. Our findings could be used to inform future studies of the effect of antibiotic treatment on the microbiota in infants with cystic fibrosis, and could assist in the prevention of early disease progression in infants with this disorder. FUNDING: Swiss National Science Foundation, Fondation Botnar, the Swiss Society for Cystic Fibrosis, and the Swiss Lung Association Bern.
BACKGROUND:Respiratory tract infections and subsequent airway inflammation occur early in the life of infants with cystic fibrosis. However, detailed information about the microbial composition of the respiratory tract in infants with this disorder is scarce. We aimed to undertake longitudinal in-depth characterisation of the upper respiratory tract microbiota in infants with cystic fibrosis during the first year of life. METHODS: We did this prospective cohort study at seven cystic fibrosis centres in Switzerland. Between Feb 1, 2011, and May 31, 2014, we enrolled 30 infants with a diagnosis of cystic fibrosis. Microbiota characterisation was done with 16S rRNA gene pyrosequencing and oligotyping of nasal swabs collected every 2 weeks from the infants with cystic fibrosis. We compared these data with data for an age-matched cohort of 47 healthy infants. We additionally investigated the effect of antibiotic treatment on the microbiota of infants with cystic fibrosis. Statistical methods included regression analyses with a multivariable multilevel linear model with random effects to correct for clustering on the individual level. FINDINGS: We analysed 461 nasal swabs taken from the infants with cystic fibrosis; the cohort of healthy infants comprised 872 samples. The microbiota of infants with cystic fibrosis differed compositionally from that of healthy infants (p=0·001). This difference was also found in exclusively antibiotic-naive samples (p=0·001). The disordering was mainly, but not solely, due to an overall increase in the mean relative abundance of Staphylococcaceae in infants with cystic fibrosis compared with healthy infants (multivariable linear regression model stratified by age and adjusted for season; second month: coefficient 16·2 [95% CI 0·6-31·9]; p=0·04; third month: 17·9 [3·3-32·5]; p=0·02; fourth month: 21·1 [7·8-34·3]; p=0·002). Oligotyping analysis enabled differentiation between Staphylococcus aureus and coagulase-negative Staphylococci. Whereas the analysis showed a decrease in S aureus at and after antibiotic treatment, coagulase-negative Staphylococci increased. INTERPRETATION: Our study describes compositional differences in the microbiota of infants with cystic fibrosis compared with healthy controls, and disordering of the microbiota on antibiotic administration. Besides S aureus, coagulase-negative Staphylococci also contributed to the disordering identified in these infants. These findings are clinically important in view of the crucial role that bacterial pathogens have in the disease progression of cystic fibrosis in early life. Our findings could be used to inform future studies of the effect of antibiotic treatment on the microbiota in infants with cystic fibrosis, and could assist in the prevention of early disease progression in infants with this disorder. FUNDING: Swiss National Science Foundation, Fondation Botnar, the Swiss Society for Cystic Fibrosis, and the Swiss Lung Association Bern.
Authors: Jessica E Pittman; Kristine M Wylie; Kathryn Akers; Gregory A Storch; Joseph Hatch; Jane Quante; Katherine B Frayman; Nadeene Clarke; Miriam Davis; Stephen M Stick; Graham L Hall; Gregory Montgomery; Sarath Ranganathan; Stephanie D Davis; Thomas W Ferkol Journal: Ann Am Thorac Soc Date: 2017-10
Authors: Katherine B Frayman; Kristine M Wylie; David S Armstrong; Rosemary Carzino; Stephanie D Davis; Thomas W Ferkol; Keith Grimwood; Gregory A Storch; Sarath C Ranganathan Journal: J Cyst Fibros Date: 2018-12-21 Impact factor: 5.482
Authors: Brett R Loman; Chandra L Shrestha; Rohan Thompson; Judith A Groner; Asuncion Mejias; Kathryn L Ruoff; George A O'Toole; Michael T Bailey; Benjamin T Kopp Journal: Pediatr Pulmonol Date: 2020-04-10
Authors: Sarath C Ranganathan; Graham L Hall; Peter D Sly; Stephen M Stick; Tonia A Douglas Journal: Am J Respir Crit Care Med Date: 2017-06-15 Impact factor: 21.405