Maartje Kristensen1, Sabine M P J Prevaes2, Gino Kalkman3, Gerdien A Tramper-Stranders4, Raiza Hasrat5, Karin M de Winter-de Groot2, Hettie M Janssens6, Harm A Tiddens6, Mireille van Westreenen7, Elisabeth A M Sanders8, Bert Arets2, Bart Keijser3, Cornelis K van der Ent2, Debby Bogaert9. 1. Department of Pediatric pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands. Electronic address: m.i.kristensen@umcutrecht.nl. 2. Department of Pediatric pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands. 3. Microbiology and Systems Biology, TNO, Zeist, the Netherlands. 4. Department of paediatrics, Fransiscus Gasthuis & Vlietland, Rotterdam, the Netherlands. 5. Department of Pediatric infectious diseases and immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands. 6. Department of Pediatric Pulmonology and Allergology, Sophia Children's Hospital, Erasmus University Medical Center, the Netherlands. 7. Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, the Netherlands. 8. Department of Pediatric infectious diseases and immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, the Netherlands. 9. Department of Pediatric infectious diseases and immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; The Queen's Medical Research Institute, University of Edinburgh, United Kingdom. Electronic address: D.Bogaert@ed.ac.uk.
Abstract
OBJECTIVES: Patients with Cystic Fibrosis (CF) suffer from pancreatic insufficiency, lipid malabsorption and gastrointestinal complaints, next to progressive pulmonary disease. Altered mucosal homoeostasis due to malfunctioning chloride channels results in an adapted microbial composition of the gastrointestinal and the respiratory tract. Additionally, antibiotic treatment has the potential to distort resident microbial communities dramatically. This study aims to investigate early life development of the gut microbial community composition of children with CF compared to healthy infants and to study the independent effects of antibiotics taking into account other clinical and lifestyle factors. STUDY DESIGN: Faecal samples from 20 infants with CF and 45 healthy infants were collected regularly during the first 18 months of life and microbial composition was determined using 16S rRNA based sequencing. RESULTS: We observed significant differences in the overall microbiota composition between infants with CF and healthy infants (p<0.001). Akkermansia and Anaerostipes were significantly more abundant in control infants, whereas Streptococci and E. coli were significantly more abundant in infants with CF, also after correction for several clinical factors (p<0.05). Antibiotic use in infants with CF was associated with a lower alpha diversity, a reduced abundance of Bifidobacterium and Bacteroides, and a higher abundance of Enterococcus. CONCLUSION: Microbial development of the gut is different in infants with CF compared to healthy infants from the first months of life on, and further deviates over time, in part as a result of antibiotic treatment. The resulting dysbiosis may have significant functional consequences for the microbial ecosystem in CF patients.
OBJECTIVES:Patients with Cystic Fibrosis (CF) suffer from pancreatic insufficiency, lipid malabsorption and gastrointestinal complaints, next to progressive pulmonary disease. Altered mucosal homoeostasis due to malfunctioning chloride channels results in an adapted microbial composition of the gastrointestinal and the respiratory tract. Additionally, antibiotic treatment has the potential to distort resident microbial communities dramatically. This study aims to investigate early life development of the gut microbial community composition of children with CF compared to healthy infants and to study the independent effects of antibiotics taking into account other clinical and lifestyle factors. STUDY DESIGN: Faecal samples from 20 infants with CF and 45 healthy infants were collected regularly during the first 18 months of life and microbial composition was determined using 16S rRNA based sequencing. RESULTS: We observed significant differences in the overall microbiota composition between infants with CF and healthy infants (p<0.001). Akkermansia and Anaerostipes were significantly more abundant in control infants, whereas Streptococci and E. coli were significantly more abundant in infants with CF, also after correction for several clinical factors (p<0.05). Antibiotic use in infants with CF was associated with a lower alpha diversity, a reduced abundance of Bifidobacterium and Bacteroides, and a higher abundance of Enterococcus. CONCLUSION: Microbial development of the gut is different in infants with CF compared to healthy infants from the first months of life on, and further deviates over time, in part as a result of antibiotic treatment. The resulting dysbiosis may have significant functional consequences for the microbial ecosystem in CF patients.