The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

Xuanji Li; Jakob Stokholm; Asker Brejnrod; Gisle Alberg Vestergaard; Jakob Russel; Urvish Trivedi; Jonathan Thorsen; Shashank Gupta; Mathis Hjort Hjelmsø; Shiraz A. Shah; Morten Arendt Rasmussen; Hans Bisgaard; Søren Johannes Sørensen

doi:10.1016/j.chom.2021.03.017

The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

Xuanji Li, Jakob Stokholm, Asker Brejnrod, Gisle Alberg Vestergaard, Jakob Russel, Urvish Trivedi, Jonathan Thorsen, Shashank Gupta, Mathis Hjort Hjelmsø, Shiraz A. Shah, Morten Arendt Rasmussen, Hans Bisgaard, Søren Johannes Sørensen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.

Original language	English
Journal	Cell Host and Microbe
Volume	29
Issue number	6
Pages (from-to)	975-987
ISSN	1931-3128
DOIs	https://doi.org/10.1016/j.chom.2021.03.017
Publication status	Published - 2021

Bibliographical note

Funding Information:
We express our deepest gratitude to the children and families of the COPSAC2010 cohort study for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. COPSAC is funded by private and public research funds all listed on www.copsac.com . The Lundbeck Foundation (grant no. R16-A1694 ), the Danish Ministry of Health (grant no. 903516 ), the Danish Council for Strategic Research (grant no. 0603-00280B ), and the Capital Region Research Foundation have provided core support for COPSAC. The Lundbeck Foundation supported 16S rRNA gene amplicon sequencing and data analysis (grant nos. R93-A8499 and R180-2014-3356 ). The Novo Nordisk Foundation supported metagenomics sequencing and analysis (grant no. NNF17OC0025014 ). X.L., J.R., U.T., and S.G. are supported by the Novo Nordisk Foundation grant ( NNF17OC0025014 ) to S.J.S. and H.B. J.T. is supported by the BRIDGE— Translational Excellence Programme (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant no. NNF18SA0034956 ). J.S. is funded by the Danish Council for Independent Research . No pharmaceutical company was involved in the study. Metagenomics analysis described in this paper was performed by Computerome. We would like to acknowledge that the cover figure was created using BioRender— biorender.com platform.

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Li, X., Stokholm, J., Brejnrod, A., Vestergaard, G. A., Russel, J., Trivedi, U., Thorsen, J., Gupta, S., Hjelmsø, M. H., Shah, S. A., Rasmussen, M. A., Bisgaard, H., & Sørensen, S. J. (2021). The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition. Cell Host and Microbe, 29(6), 975-987. https://doi.org/10.1016/j.chom.2021.03.017

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title = "The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition",

abstract = "Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.",

author = "Xuanji Li and Jakob Stokholm and Asker Brejnrod and Vestergaard, {Gisle Alberg} and Jakob Russel and Urvish Trivedi and Jonathan Thorsen and Shashank Gupta and Hjelms{\o}, {Mathis Hjort} and Shah, {Shiraz A.} and Rasmussen, {Morten Arendt} and Hans Bisgaard and S{\o}rensen, {S{\o}ren Johannes}",

note = "Funding Information: We express our deepest gratitude to the children and families of the COPSAC2010 cohort study for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. COPSAC is funded by private and public research funds all listed on www.copsac.com . The Lundbeck Foundation (grant no. R16-A1694 ), the Danish Ministry of Health (grant no. 903516 ), the Danish Council for Strategic Research (grant no. 0603-00280B ), and the Capital Region Research Foundation have provided core support for COPSAC. The Lundbeck Foundation supported 16S rRNA gene amplicon sequencing and data analysis (grant nos. R93-A8499 and R180-2014-3356 ). The Novo Nordisk Foundation supported metagenomics sequencing and analysis (grant no. NNF17OC0025014 ). X.L., J.R., U.T., and S.G. are supported by the Novo Nordisk Foundation grant ( NNF17OC0025014 ) to S.J.S. and H.B. J.T. is supported by the BRIDGE— Translational Excellence Programme (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant no. NNF18SA0034956 ). J.S. is funded by the Danish Council for Independent Research . No pharmaceutical company was involved in the study. Metagenomics analysis described in this paper was performed by Computerome. We would like to acknowledge that the cover figure was created using BioRender— biorender.com platform. ",

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doi = "10.1016/j.chom.2021.03.017",

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Li, X, Stokholm, J, Brejnrod, A, Vestergaard, GA, Russel, J, Trivedi, U, Thorsen, J, Gupta, S, Hjelmsø, MH, Shah, SA, Rasmussen, MA, Bisgaard, H & Sørensen, SJ 2021, 'The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition', Cell Host and Microbe, vol. 29, no. 6, pp. 975-987. https://doi.org/10.1016/j.chom.2021.03.017

TY - JOUR

T1 - The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

AU - Li, Xuanji

AU - Stokholm, Jakob

AU - Brejnrod, Asker

AU - Vestergaard, Gisle Alberg

AU - Russel, Jakob

AU - Trivedi, Urvish

AU - Thorsen, Jonathan

AU - Gupta, Shashank

AU - Hjelmsø, Mathis Hjort

AU - Shah, Shiraz A.

AU - Rasmussen, Morten Arendt

AU - Bisgaard, Hans

AU - Sørensen, Søren Johannes

N1 - Funding Information: We express our deepest gratitude to the children and families of the COPSAC2010 cohort study for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. COPSAC is funded by private and public research funds all listed on www.copsac.com . The Lundbeck Foundation (grant no. R16-A1694 ), the Danish Ministry of Health (grant no. 903516 ), the Danish Council for Strategic Research (grant no. 0603-00280B ), and the Capital Region Research Foundation have provided core support for COPSAC. The Lundbeck Foundation supported 16S rRNA gene amplicon sequencing and data analysis (grant nos. R93-A8499 and R180-2014-3356 ). The Novo Nordisk Foundation supported metagenomics sequencing and analysis (grant no. NNF17OC0025014 ). X.L., J.R., U.T., and S.G. are supported by the Novo Nordisk Foundation grant ( NNF17OC0025014 ) to S.J.S. and H.B. J.T. is supported by the BRIDGE— Translational Excellence Programme (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant no. NNF18SA0034956 ). J.S. is funded by the Danish Council for Independent Research . No pharmaceutical company was involved in the study. Metagenomics analysis described in this paper was performed by Computerome. We would like to acknowledge that the cover figure was created using BioRender— biorender.com platform.

PY - 2021

Y1 - 2021

N2 - Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.

AB - Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.

U2 - 10.1016/j.chom.2021.03.017

DO - 10.1016/j.chom.2021.03.017

M3 - Journal article

C2 - 33887206

AN - SCOPUS:85106315800

SN - 1931-3128

VL - 29

SP - 975

EP - 987

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 6

ER -

The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

Abstract

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