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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	American English
Pages (from-to)	4921-4936.e15
Journal	Cell
Volume	185
Issue number	26
DOIs	https://doi.org/10.1016/j.cell.2022.11.023
State	Published - 22 Dec 2022

Bibliographical note

Funding Information:
We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health ( P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation ( 2-SRA-2016-247-S-B ), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research.

Funding Information:
We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health (P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation (2-SRA-2016-247-S-B), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research. T.V. H.V. M.K. and R.J.X. served as principal investigators. T.V. and K.S.J. analyzed metagenomic data. T.V. K.S.J. J.A.-P. M.S. C.B.C. and D.R.P. analyzed metabolomic data. T.R. analyzed intestinal biomarkers. J.H. analyzed cytokines. T.R. J.H. H.S. S.O. H.H. J.I. S.M.V. and M.K. contributed to collection of stool and blood samples and patient information. M.Y. and C.M.M. collected breast milk samples. T.V. K.S.J. D.R.P. H.V. and R.J.X. drafted the manuscript. All authors discussed the results, critically reviewed the text, and approved the final manuscript. R.J.X. is co-founder of Jnana Therapeutics and Celsius Therapeutics, board director at MoonLake Immunotherapeutics, and consultant to Nestlé; these organizations had no role in the study.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

gut metabolome
horizontal gene transfer
infant gut microbiome
mother-to-infant microbiome transmission

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10.1016/j.cell.2022.11.023

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Vatanen, T., Jabbar, K. S., Ruohtula, T., Honkanen, J., Avila-Pacheco, J., Siljander, H., Stražar, M., Oikarinen, S., Hyöty, H., Ilonen, J., Mitchell, C. M., Yassour, M., Virtanen, S. M., Clish, C. B., Plichta, D. R., Vlamakis, H., Knip, M., & Xavier, R. J. (2022). Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism. Cell, 185(26), 4921-4936.e15. https://doi.org/10.1016/j.cell.2022.11.023

@article{dcefe45085ba4e55aba8ee47273ed596,

title = "Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism",

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",

author = "Tommi Vatanen and Jabbar, {Karolina S.} and Terhi Ruohtula and Jarno Honkanen and Julian Avila-Pacheco and Heli Siljander and Martin Stra{\v z}ar and Sami Oikarinen and Heikki Hy{\"o}ty and Jorma Ilonen and Mitchell, {Caroline M.} and Moran Yassour and Virtanen, {Suvi M.} and Clish, {Clary B.} and Plichta, {Damian R.} and Hera Vlamakis and Mikael Knip and Xavier, {Ramnik J.}",

note = "Funding Information: We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health ( P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation ( 2-SRA-2016-247-S-B ), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research. Funding Information: We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health (P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation (2-SRA-2016-247-S-B), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research. T.V. H.V. M.K. and R.J.X. served as principal investigators. T.V. and K.S.J. analyzed metagenomic data. T.V. K.S.J. J.A.-P. M.S. C.B.C. and D.R.P. analyzed metabolomic data. T.R. analyzed intestinal biomarkers. J.H. analyzed cytokines. T.R. J.H. H.S. S.O. H.H. J.I. S.M.V. and M.K. contributed to collection of stool and blood samples and patient information. M.Y. and C.M.M. collected breast milk samples. T.V. K.S.J. D.R.P. H.V. and R.J.X. drafted the manuscript. All authors discussed the results, critically reviewed the text, and approved the final manuscript. R.J.X. is co-founder of Jnana Therapeutics and Celsius Therapeutics, board director at MoonLake Immunotherapeutics, and consultant to Nestl{\'e}; these organizations had no role in the study. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = dec,

day = "22",

doi = "10.1016/j.cell.2022.11.023",

language = "American English",

volume = "185",

pages = "4921--4936.e15",

journal = "Cell",

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Vatanen, T, Jabbar, KS, Ruohtula, T, Honkanen, J, Avila-Pacheco, J, Siljander, H, Stražar, M, Oikarinen, S, Hyöty, H, Ilonen, J, Mitchell, CM, Yassour, M, Virtanen, SM, Clish, CB, Plichta, DR, Vlamakis, H, Knip, M & Xavier, RJ 2022, 'Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism', Cell, vol. 185, no. 26, pp. 4921-4936.e15. https://doi.org/10.1016/j.cell.2022.11.023

TY - JOUR

T1 - Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism

AU - Vatanen, Tommi

AU - Jabbar, Karolina S.

AU - Ruohtula, Terhi

AU - Honkanen, Jarno

AU - Avila-Pacheco, Julian

AU - Siljander, Heli

AU - Stražar, Martin

AU - Oikarinen, Sami

AU - Hyöty, Heikki

AU - Ilonen, Jorma

AU - Mitchell, Caroline M.

AU - Yassour, Moran

AU - Virtanen, Suvi M.

AU - Clish, Clary B.

AU - Plichta, Damian R.

AU - Vlamakis, Hera

AU - Knip, Mikael

AU - Xavier, Ramnik J.

N1 - Funding Information: We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health ( P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation ( 2-SRA-2016-247-S-B ), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research. Funding Information: We thank Tiffany Poon, Luke Besse, and Timothy Arthur for sample and data management and Theresa Reimels for editorial assistance and figure preparation. This work was funded by the National Institutes of Health (P30 DK043351 to R.J.X.), Juvenile Diabetes Research Foundation (2-SRA-2016-247-S-B), Center for Microbiome Informatics and Therapeutics, and Wallenberg Foundations (to K.S.J.). M.Y. is the Rosalind, Paul and Robin Berlin Faculty Development Chair in Perinatal Research. T.V. H.V. M.K. and R.J.X. served as principal investigators. T.V. and K.S.J. analyzed metagenomic data. T.V. K.S.J. J.A.-P. M.S. C.B.C. and D.R.P. analyzed metabolomic data. T.R. analyzed intestinal biomarkers. J.H. analyzed cytokines. T.R. J.H. H.S. S.O. H.H. J.I. S.M.V. and M.K. contributed to collection of stool and blood samples and patient information. M.Y. and C.M.M. collected breast milk samples. T.V. K.S.J. D.R.P. H.V. and R.J.X. drafted the manuscript. All authors discussed the results, critically reviewed the text, and approved the final manuscript. R.J.X. is co-founder of Jnana Therapeutics and Celsius Therapeutics, board director at MoonLake Immunotherapeutics, and consultant to Nestlé; these organizations had no role in the study. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/12/22

Y1 - 2022/12/22

N2 - 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.

AB - 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.

KW - gut metabolome

KW - horizontal gene transfer

KW - infant gut microbiome

KW - mother-to-infant microbiome transmission

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U2 - 10.1016/j.cell.2022.11.023

DO - 10.1016/j.cell.2022.11.023

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AN - SCOPUS:85144246023

SN - 0092-8674

VL - 185

SP - 4921-4936.e15

JO - Cell

JF - Cell

IS - 26

ER -

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

Abstract

Bibliographical note

Keywords

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