title: Gut resistome development in healthy twin pairs in the first year of life.
abstract: BACKGROUND
  The early life of the human host marks a critically important time for establishment of the gut microbial community, yet the developmental trajectory of gut community-encoded resistance genes (resistome) is unknown. We present a longitudinal study of the fecal antibiotic resistome of healthy amoxicillin-exposed and antibiotic-naive twins and their mothers during the first year of life.
  
  
  RESULTS
  We extracted metagenomic DNA (mgDNA) from fecal samples collected from three healthy twin pairs at three timepoints (1 or 2 months, 6 or 7 months, and 11 months) and from their mothers (collected at delivery). The mgDNA was used to construct metagenomic expression libraries in an Escherichia coli host. These libraries were screened for antibiotic resistance, and functionally selected resistance genes were sequenced and annotated. A diverse fecal resistome distinct from the maternal resistome was apparent by 2 months of age, and infants' fecal resistomes included resistance to clinically important broad-spectrum beta-lactam antibiotics (e.g., piperacillin-tazobactam, aztreonam, cefepime) not found in their mothers. Dissemination of resistance genes among members of a given family was positively correlated with sharing of those same resistance genes between unrelated families, potentially identifying within-family sharing as a marker of resistance genes emerging in the human community at large. Finally, we found a distinct developmental trajectory for a community-encoded function: chloramphenicol resistance. All study subjects at all timepoints harbored chloramphenicol resistance determinants, but multidrug efflux pumps (rarely found in mothers) were the primary effectors of chloramphenicol resistance in young infants. Chloramphenicol acetyltransferases were more common in mothers than in infants and were found in nearly all the infants at later timepoints.
  
  
  CONCLUSIONS
  Our results suggest that healthy 1-2-month-old infants' gut microbes harbor clinically relevant resistance genes distinct from those of their mothers, and that family-specific shared environmental factors early in life shape resistome development.
authors.affiliation: Department of Pediatrics, Washington University in St Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Moore
authors.affiliation: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Ahmadi
authors.affiliation: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA.
authors.forename: Sanket
authors.initials: S
authors.lastname: Patel
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA.
authors.forename: Molly K
authors.initials: MK
authors.lastname: Gibson
authors.affiliation: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Washington University in St Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
authors.forename: Malick I
authors.initials: MI
authors.lastname: Ndao
authors.affiliation: Department of Biostatistics, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Deych
authors.affiliation: Department of Biostatistics, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
authors.forename: William
authors.initials: W
authors.lastname: Shannon
authors.affiliation: Department of Pediatrics, Washington University in St Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Department of Molecular Microbiology, Washington University in St. School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
authors.affiliation: Department of Pediatrics, Washington University in St Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Warner
authors.affiliation: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110 USA ; Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, 4444 Forest Park Boulevard, St. Louis, MO 63108 USA ; Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130 USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Dantas
keywords: Antibiotic resistance; Beta lactamase; Chloramphenicol resistance; Fecal microbiome; Gut microbiome; Pediatrics