Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability.
The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little is known about the impact of environmental factors on the developing human gut microbiome. We report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, about half of whom received multiple courses of antibiotics during the first 3 years of life. Whereas the gut microbiome of most children born by vaginal delivery was dominated by Bacteroides species, the four children born by cesarean section and about 20% of vaginally born children lacked Bacteroides in the first 6 to 18 months of life. Longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed detection of strain-level variation as well as the abundance of antibiotic resistance genes. The microbiota of antibiotic-treated children was less diverse in terms of both bacterial species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. Antibiotic resistance genes carried on microbial chromosomes showed a peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes carried on mobile elements persisted longer after antibiotic therapy ended. Our results highlight the value of high-density longitudinal sampling studies with high-resolution strain profiling for studying the establishment and response to perturbation of the infant gut microbiome.
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Moran
M
Yassour
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA. Department of Computer Science, Aalto University School of Science, 02150 Espoo, Finland.
Tommi
T
Vatanen
Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland. Department of Pediatrics, Tampere University Hospital, 33521 Tampere, Finland.
Heli
H
Siljander
Department of Pediatrics, Jorvi Hospital, Helsinki University Hospital, 02740 Espoo, Finland.
Anu-Maaria
AM
Hämäläinen
Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.
Taina
T
Härkönen
Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.
Samppa J
SJ
Ryhänen
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
Eric A
EA
Franzosa
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA.
Hera
H
Vlamakis
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA. Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
Curtis
C
Huttenhower
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA.
Dirk
D
Gevers
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA. Department of Biology, MIT, Cambridge, MA 02139, USA. Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.
Eric S
ES
Lander
Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland. Department of Pediatrics, Tampere University Hospital, 33521 Tampere, Finland. Folkhälsan Research Center, 00290 Helsinki, Finland.
Mikael
M
Knip
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, MA 02142, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA 02139, USA. xavier@molbio.mgh.harvard.edu.
Ramnik J
RJ
Xavier
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001439:Bacteroides / Q000187:drug effects / Q000235:genetics; D002585:Cesarean Section; D002675:Child, Preschool; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male
D000900:Anti-Bacterial Agents