title: Intestinal microbiota composition after antibiotic treatment in early life: the INCA study.
abstract: BACKGROUND
  The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life.
  
  
  METHODS
  450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics.
  
  
  CONCLUSIONS
  Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can restore the ecological balance of the microbiota and may mitigate potential negative effects on the developing immune system, when use of antibiotics cannot be avoided.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02536560. Registered 28 August 2015.
authors.affiliation: Department of Pediatrics, St Antonius Hospital, PO Box 2500, 3430 EM, Nieuwegein, The Netherlands. n.rutten@antoniusziekenhuis.nl.
authors.forename: N B M M
authors.initials: NB
authors.lastname: Rutten
authors.affiliation: Department of Sciences, University College Roosevelt Academy, PO Box 94, 4330 AB, Middelburg, The Netherlands. g.rijkers@ucr.nl.
authors.forename: G T
authors.initials: GT
authors.lastname: Rijkers
authors.affiliation: Department of Pediatrics, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands. CB.Meijssen@meandermc.nl.
authors.forename: C B
authors.initials: CB
authors.lastname: Meijssen
authors.affiliation: Department of Pediatrics, Tergooi Hospital, Rijksstraatweg 1, 1261 AN, Blaricum, The Netherlands. cecrijns@yahoo.com.
authors.forename: C E
authors.initials: CE
authors.lastname: Crijns
authors.affiliation: Department of Pediatrics, Gelre Hospitals, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn, The Netherlands. a.oudshoorn@gelre.nl.
authors.forename: J H
authors.initials: JH
authors.lastname: Oudshoorn
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital/University Medical Center, Lundlaan 6, 3584 EA, Utrecht, The Netherlands. K.vanderEnt@umcutrecht.nl.
authors.forename: C K
authors.initials: CK
authors.lastname: van der Ent
authors.affiliation: Department of Pediatrics, St Antonius Hospital, PO Box 2500, 3430 EM, Nieuwegein, The Netherlands. a.vlieger@antoniusziekenhuis.nl.
authors.forename: A M
authors.initials: AM
authors.lastname: Vlieger
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D007239:Infections / Q000188:drug therapy* / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D008297:Male; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents