title: The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.
abstract: Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors: Aleksandar D
authors: AD
authors: Kostic
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors: Dirk
authors: D
authors: Gevers
authors: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.
authors: Heli
authors: H
authors: Siljander
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Information and Computer Science, Aalto University School of Science, 02150 Espoo, Finland.
authors: Tommi
authors: T
authors: Vatanen
authors: Steno Diabetes Center, 2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, 02044 Espoo, Finland.
authors: Tuulia
authors: T
authors: Hyötyläinen
authors: Department of Pediatrics, Jorvi Hospital, 02740 Espoo, Finland.
authors: Anu-Maaria
authors: AM
authors: Hämäläinen
authors: Department of Pediatrics, University of Tartu, Estonia and Tartu University Hospital, 51014 Tartu, Estonia.
authors: Aleksandr
authors: A
authors: Peet
authors: Department of Pediatrics, University of Tartu, Estonia and Tartu University Hospital, 51014 Tartu, Estonia.
authors: Vallo
authors: V
authors: Tillmann
authors: Faculty of Pharmacy, University of Helsinki, 00290 Helsinki, Finland; VTT Technical Research Centre of Finland, 02044 Espoo, Finland.
authors: Päivi
authors: P
authors: Pöhö
authors: Steno Diabetes Center, 2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, 02044 Espoo, Finland.
authors: Ismo
authors: I
authors: Mattila
authors: Department of Information and Computer Science, Aalto University School of Science, 02150 Espoo, Finland.
authors: Harri
authors: H
authors: Lähdesmäki
authors: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors: Eric A
authors: EA
authors: Franzosa
authors: Research Program Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.
authors: Outi
authors: O
authors: Vaarala
authors: Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, 9713 GZ Groningen, the Netherlands.
authors: Marcus
authors: M
authors: de Goffau
authors: Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, 9713 GZ Groningen, the Netherlands.
authors: Hermie
authors: H
authors: Harmsen
authors: Immunogenetics Laboratory, University of Turku, 20520 Turku, Finland; Department of Clinical Microbiology, University of Eastern Finland, 70211 Kuopio, Finland.
authors: Jorma
authors: J
authors: Ilonen
authors: Department of Lifestyle and Participation, National Institute for Health and Welfare, 00271 Helsinki, Finland; School of Health Sciences, University of Tampere, 33014 Tampere, Finland; Science Centre, Pirkanmaa Hospital District, 33521 Tampere, Finland.
authors: Suvi M
authors: SM
authors: Virtanen
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors: Clary B
authors: CB
authors: Clish
authors: Steno Diabetes Center, 2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, 02044 Espoo, Finland.
authors: Matej
authors: M
authors: Orešič
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors: Curtis
authors: C
authors: Huttenhower
authors: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland; Folkhälsan Research Center, 00290 Helsinki, Finland; Department of Pediatrics, Tampere University Hospital, 33521 Tampere, Finland.
authors: Mikael
authors: M
authors: Knip
authors: Broad Institute of MIT and Harvard, 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, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
authors: Ramnik J
authors: RJ
authors: Xavier
mesh_terms: D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007223:Infant