title: Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants.
abstract: OBJECTIVE
  The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula.
  
  
  OBJECTIVE
  To examine the associations of delivery mode and feeding method with infant intestinal microbiome composition at approximately 6 weeks of life.
  
  
  METHODS
  Prospective observational study of 102 infants followed up as part of a US pregnancy cohort study.
  
  
  METHODS
  Delivery mode was abstracted from delivery medical records, and feeding method prior to the time of stool collection was ascertained through detailed questionnaires.
  
  
  METHODS
  Stool microbiome composition was characterized using next-generation sequencing of the 16S rRNA gene.
  
  
  RESULTS
  There were 102 infants (mean gestational age, 39.7 weeks; range, 37.1-41.9 weeks) included in this study, of whom 70 were delivered vaginally and 32 by cesarean delivery. In the first 6 weeks of life, 70 were exclusively breastfed, 26 received combination feeding, and 6 were exclusively formula fed. We identified independent associations between microbial community composition and both delivery mode (P< .001; Q < .001) and feeding method (P = .01; Q < .001). Differences in microbial community composition between vaginally delivered infants and infants delivered by cesarean birth were equivalent to or significantly larger than those between feeding groups (P = .003). Bacterial communities associated with combination feeding were more similar to those associated with exclusive formula feeding than exclusive breastfeeding (P = .002). We identified 6 individual bacterial genera that were differentially abundant between delivery mode and feeding groups.
  
  
  CONCLUSIONS
  The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital at Dartmouth, Lebanon, New Hampshire2Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire.
authors.forename: Juliette C
authors.initials: JC
authors.lastname: Madan
authors.affiliation: Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire3Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire4Computational Genetics Laboratory, Geisel School of.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Hoen
authors.affiliation: Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Lundgren
authors.affiliation: Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire3Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Shohreh F
authors.initials: SF
authors.lastname: Farzan
authors.affiliation: Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire5Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Cottingham
authors.affiliation: Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors.forename: Hilary G
authors.initials: HG
authors.lastname: Morrison
authors.affiliation: Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Sogin
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Computational Genetics Laboratory, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire8Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.affiliation: Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire3Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire9Center for Molecular Epidemiology, The Geisel School.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
mesh_terms: D000293:Adolescent; D000328:Adult; D001903:Bottle Feeding; D001942:Breast Feeding; D002585:Cesarean Section; D005243:Feces / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007422:Intestines / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011446:Prospective Studies; D055815:Young Adult