Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism

Tommi Vatanen; Karolina S Jabbar; Terhi Ruohtula; Jarno Honkanen; Julian Avila-Pacheco; Heli Siljander; Martin Stražar; Sami Oikarinen; Heikki Hyöty; Jorma Ilonen; Caroline M Mitchell; Moran Yassour; Suvi M Virtanen; Clary B Clish; Damian R Plichta; Hera Vlamakis; Mikael Knip; Ramnik J Xavier

doi:10.1016/j.cell.2022.11.023

Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism

Cell. 2022 Dec 22;185(26):4921-4936.e15. doi: 10.1016/j.cell.2022.11.023.

Authors

Tommi Vatanen¹, Karolina S Jabbar², Terhi Ruohtula³, Jarno Honkanen³, Julian Avila-Pacheco², Heli Siljander⁴, Martin Stražar², Sami Oikarinen⁵, Heikki Hyöty⁶, Jorma Ilonen⁷, Caroline M Mitchell⁸, Moran Yassour⁹, Suvi M Virtanen¹⁰, Clary B Clish², Damian R Plichta¹¹, Hera Vlamakis¹¹, Mikael Knip¹², Ramnik J Xavier¹³

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Liggins Institute, University of Auckland, Auckland, New Zealand.
² Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ New Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
⁴ New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Centre for Military Medicine, Finnish Defence Forces, Riihimäki, Finland.
⁵ Department of Virology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ Department of Virology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Fimlab Laboratories, Tampere, Finland.
⁷ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
⁸ Vincent Obstetrics & Gynecology Department, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹ Microbiology & Molecular Genetics Department, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
¹⁰ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Center for Child Health Research and Development and Innovation Center, Tampere University Hospital, Tampere, Finland.
¹¹ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA 02139, USA.
¹² Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
¹³ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA 02139, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.

Abstract

The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative analysis expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.

Keywords: gut metabolome; horizontal gene transfer; infant gut microbiome; mother-to-infant microbiome transmission.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Breast Feeding
Feces
Female
Gastrointestinal Microbiome* / genetics
Humans
Infant
Interspersed Repetitive Sequences
Microbiota* / genetics
Mothers
Pregnancy

Grants and funding

P30 DK043351/DK/NIDDK NIH HHS/United States