Gut microbiota development during infancy: Impact of introducing allergenic foods

Tom Marrs; Jay Hyun Jo; Michael R. Perkin; Damian W. Rivett; Adam A. Witney; Kenneth D. Bruce; Kirsty Logan; Joanna Craven; Suzana Radulovic; Serge A. Versteeg; Ronald van Ree; W. H. Irwin McLean; David P. Strachan; Gideon Lack; Heidi H. Kong; Carsten Flohr

doi:10.1016/j.jaci.2020.09.042

Gut microbiota development during infancy: Impact of introducing allergenic foods

Tom Marrs, Jay Hyun Jo, Michael R. Perkin, Damian W. Rivett, Adam A. Witney, Kenneth D. Bruce, Kirsty Logan, Joanna Craven, Suzana Radulovic, Serge A. Versteeg, Ronald van Ree, W. H. Irwin McLean, David P. Strachan, Gideon Lack, Heidi H. Kong, Carsten Flohr (Lead / Corresponding author)

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Abstract

Background: The gut microbiota potentially plays an important role in the immunologic education of the host during early infancy.

Objective: We sought to determine how the infant gut microbiota evolve during infancy, particularly in relation to hygiene-related environmental factors, atopic disorders, and a randomized introduction of allergenic solids.

Methods: A total of 1303 exclusively breast-fed infants were enrolled in a dietary randomized controlled trial (Enquiring About Tolerance study) from 3 months of age. In this nested longitudinal study, fecal samples were collected at baseline, with additional sampling of selected cases and controls at 6 and 12 months to study the evolution of their gut microbiota, using 16S ribosomal RNA gene-targeted amplicon sequencing.

Results: In the 288 baseline samples from exclusively breast-fed infant at 3 months, the gut microbiota was highly heterogeneous, forming 3 distinct clusters: Bifidobacterium-rich, Bacteroides-rich, and Escherichia/Shigella-rich. Mode of delivery was the major discriminating factor. Increased Clostridium sensu stricto relative abundance at 3 months was associated with presence of atopic dermatitis on examination at age 3 and 12 months. From the selected cases and controls with longitudinal samples (n = 70), transition to Bacteroides-rich communities and influx of adult-specific microbes were observed during the first year of life. The introduction of allergenic solids promoted a significant increase in Shannon diversity and representation of specific microbes, such as genera belonging to Prevotellaceae and Proteobacteria (eg, Escherichia/Shigella), as compared with infants recommended to exclusively breast-feed.

Conclusions: Specific gut microbiota characteristics of samples from 3-month-old breast-fed infants were associated with cesarean birth, and greater Clostridium sensu stricto abundance was associated with atopic dermatitis. The randomized introduction of allergenic solids from age 3 months alongside breast-feeding was associated with differential dynamics of maturation of the gut microbial communities.

Original language	English
Pages (from-to)	613-621.e9
Number of pages	18
Journal	Journal of Allergy and Clinical Immunology
Volume	147
Issue number	2
Early online date	4 Feb 2021
DOIs	https://doi.org/10.1016/j.jaci.2020.09.042
Publication status	Published - Feb 2021

Keywords

Atopic dermatitis
bacteria
colonization
diet
environment
food
microbiome
tolerance

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Marrs, T., Jo, J. H., Perkin, M. R., Rivett, D. W., Witney, A. A., Bruce, K. D., Logan, K., Craven, J., Radulovic, S., Versteeg, S. A., van Ree, R., McLean, W. H. I., Strachan, D. P., Lack, G., Kong, H. H., & Flohr, C. (2021). Gut microbiota development during infancy: Impact of introducing allergenic foods. Journal of Allergy and Clinical Immunology, 147(2), 613-621.e9. https://doi.org/10.1016/j.jaci.2020.09.042

@article{63750ada2d9346258ade16fb5301c1de,

title = "Gut microbiota development during infancy: Impact of introducing allergenic foods",

abstract = "Background: The gut microbiota potentially plays an important role in the immunologic education of the host during early infancy.Objective: We sought to determine how the infant gut microbiota evolve during infancy, particularly in relation to hygiene-related environmental factors, atopic disorders, and a randomized introduction of allergenic solids.Methods: A total of 1303 exclusively breast-fed infants were enrolled in a dietary randomized controlled trial (Enquiring About Tolerance study) from 3 months of age. In this nested longitudinal study, fecal samples were collected at baseline, with additional sampling of selected cases and controls at 6 and 12 months to study the evolution of their gut microbiota, using 16S ribosomal RNA gene-targeted amplicon sequencing.Results: In the 288 baseline samples from exclusively breast-fed infant at 3 months, the gut microbiota was highly heterogeneous, forming 3 distinct clusters: Bifidobacterium-rich, Bacteroides-rich, and Escherichia/Shigella-rich. Mode of delivery was the major discriminating factor. Increased Clostridium sensu stricto relative abundance at 3 months was associated with presence of atopic dermatitis on examination at age 3 and 12 months. From the selected cases and controls with longitudinal samples (n = 70), transition to Bacteroides-rich communities and influx of adult-specific microbes were observed during the first year of life. The introduction of allergenic solids promoted a significant increase in Shannon diversity and representation of specific microbes, such as genera belonging to Prevotellaceae and Proteobacteria (eg, Escherichia/Shigella), as compared with infants recommended to exclusively breast-feed.Conclusions: Specific gut microbiota characteristics of samples from 3-month-old breast-fed infants were associated with cesarean birth, and greater Clostridium sensu stricto abundance was associated with atopic dermatitis. The randomized introduction of allergenic solids from age 3 months alongside breast-feeding was associated with differential dynamics of maturation of the gut microbial communities.",

keywords = "Atopic dermatitis, bacteria, colonization, diet, environment, food, microbiome, tolerance",

author = "Tom Marrs and Jo, {Jay Hyun} and Perkin, {Michael R.} and Rivett, {Damian W.} and Witney, {Adam A.} and Bruce, {Kenneth D.} and Kirsty Logan and Joanna Craven and Suzana Radulovic and Versteeg, {Serge A.} and {van Ree}, Ronald and McLean, {W. H. Irwin} and Strachan, {David P.} and Gideon Lack and Kong, {Heidi H.} and Carsten Flohr",

note = "Funding Information: The main components of the Enquiring About Tolerance study were jointly funded by the UK Food Standards Agency (grant code T07051 ) and the Medical Research Council (MRC, grant no. MC_G1001205 ). The skin-related aspects of the study were supported by a Clinician Scientist Award from the UK National Institute for Health Research (NIHR) held by C.F. (NIHRCS/01/2008/009). The British Skin Foundation (BSF) funded the fecal sample sequencing work (BSF large grant 5047i, principle investigator C.F.). T.M., C.F., and G.L. are supported by the NIHR Biomedical Research Centre at Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. C.F. is also a Principle Investigator of the EU-funded IMI Consortium BIOMAP, and the work described in this project was performed within the frame of the BIOMAP project which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The McLean lab is funded by Wellcome Trust Programme (092530/Z/10/Z to W.H.I.M.) and Bioresources grants (090066/B/09/Z to W.H.I.M.). The Centre for Dermatology and Genetic Medicine, University of Dundee, is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z to W.H.I.M.). This work was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (J.-H.J., H.H.K.). J.-H.J. was also supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant no. HI15C1095). The views expressed in this publication are those of the authors and not necessarily those of the Food Standards Agency, the MRC, the NHS, the UK NIHR, the UK Department of Health, the US National Institutes of Health, or the Wellcome Trust. Funding Information: Disclosure of potential conflict of interest: G. Lack has received research funding from ALK Abello, the Immune Tolerance Network, US National Peanut Board, Food Standards Agency, Medical Research Council, Food Allergy Initiative, Action Medical Research, and Guys and St Thomas{\textquoteright} Charity; sponsorship from Novartis, Sodilac, Spanish Society of Allergy and Clinical Immunology, Danone Nutricia, and Nestle; has been a scientific advisor for DBV Technologies; and gives voluntary advice to the Anaphylaxis Campaign and US National Peanut Board. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2020 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

doi = "10.1016/j.jaci.2020.09.042",

language = "English",

volume = "147",

pages = "613--621.e9",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier",

number = "2",

}

Marrs, T, Jo, JH, Perkin, MR, Rivett, DW, Witney, AA, Bruce, KD, Logan, K, Craven, J, Radulovic, S, Versteeg, SA, van Ree, R, McLean, WHI, Strachan, DP, Lack, G, Kong, HH & Flohr, C 2021, 'Gut microbiota development during infancy: Impact of introducing allergenic foods', Journal of Allergy and Clinical Immunology, vol. 147, no. 2, pp. 613-621.e9. https://doi.org/10.1016/j.jaci.2020.09.042

TY - JOUR

T1 - Gut microbiota development during infancy

T2 - Impact of introducing allergenic foods

AU - Marrs, Tom

AU - Jo, Jay Hyun

AU - Perkin, Michael R.

AU - Rivett, Damian W.

AU - Witney, Adam A.

AU - Bruce, Kenneth D.

AU - Logan, Kirsty

AU - Craven, Joanna

AU - Radulovic, Suzana

AU - Versteeg, Serge A.

AU - van Ree, Ronald

AU - McLean, W. H. Irwin

AU - Strachan, David P.

AU - Lack, Gideon

AU - Kong, Heidi H.

AU - Flohr, Carsten

N1 - Funding Information: The main components of the Enquiring About Tolerance study were jointly funded by the UK Food Standards Agency (grant code T07051 ) and the Medical Research Council (MRC, grant no. MC_G1001205 ). The skin-related aspects of the study were supported by a Clinician Scientist Award from the UK National Institute for Health Research (NIHR) held by C.F. (NIHRCS/01/2008/009). The British Skin Foundation (BSF) funded the fecal sample sequencing work (BSF large grant 5047i, principle investigator C.F.). T.M., C.F., and G.L. are supported by the NIHR Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust and King’s College London. C.F. is also a Principle Investigator of the EU-funded IMI Consortium BIOMAP, and the work described in this project was performed within the frame of the BIOMAP project which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The McLean lab is funded by Wellcome Trust Programme (092530/Z/10/Z to W.H.I.M.) and Bioresources grants (090066/B/09/Z to W.H.I.M.). The Centre for Dermatology and Genetic Medicine, University of Dundee, is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z to W.H.I.M.). This work was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (J.-H.J., H.H.K.). J.-H.J. was also supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant no. HI15C1095). The views expressed in this publication are those of the authors and not necessarily those of the Food Standards Agency, the MRC, the NHS, the UK NIHR, the UK Department of Health, the US National Institutes of Health, or the Wellcome Trust. Funding Information: Disclosure of potential conflict of interest: G. Lack has received research funding from ALK Abello, the Immune Tolerance Network, US National Peanut Board, Food Standards Agency, Medical Research Council, Food Allergy Initiative, Action Medical Research, and Guys and St Thomas’ Charity; sponsorship from Novartis, Sodilac, Spanish Society of Allergy and Clinical Immunology, Danone Nutricia, and Nestle; has been a scientific advisor for DBV Technologies; and gives voluntary advice to the Anaphylaxis Campaign and US National Peanut Board. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2020 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - Background: The gut microbiota potentially plays an important role in the immunologic education of the host during early infancy.Objective: We sought to determine how the infant gut microbiota evolve during infancy, particularly in relation to hygiene-related environmental factors, atopic disorders, and a randomized introduction of allergenic solids.Methods: A total of 1303 exclusively breast-fed infants were enrolled in a dietary randomized controlled trial (Enquiring About Tolerance study) from 3 months of age. In this nested longitudinal study, fecal samples were collected at baseline, with additional sampling of selected cases and controls at 6 and 12 months to study the evolution of their gut microbiota, using 16S ribosomal RNA gene-targeted amplicon sequencing.Results: In the 288 baseline samples from exclusively breast-fed infant at 3 months, the gut microbiota was highly heterogeneous, forming 3 distinct clusters: Bifidobacterium-rich, Bacteroides-rich, and Escherichia/Shigella-rich. Mode of delivery was the major discriminating factor. Increased Clostridium sensu stricto relative abundance at 3 months was associated with presence of atopic dermatitis on examination at age 3 and 12 months. From the selected cases and controls with longitudinal samples (n = 70), transition to Bacteroides-rich communities and influx of adult-specific microbes were observed during the first year of life. The introduction of allergenic solids promoted a significant increase in Shannon diversity and representation of specific microbes, such as genera belonging to Prevotellaceae and Proteobacteria (eg, Escherichia/Shigella), as compared with infants recommended to exclusively breast-feed.Conclusions: Specific gut microbiota characteristics of samples from 3-month-old breast-fed infants were associated with cesarean birth, and greater Clostridium sensu stricto abundance was associated with atopic dermatitis. The randomized introduction of allergenic solids from age 3 months alongside breast-feeding was associated with differential dynamics of maturation of the gut microbial communities.

AB - Background: The gut microbiota potentially plays an important role in the immunologic education of the host during early infancy.Objective: We sought to determine how the infant gut microbiota evolve during infancy, particularly in relation to hygiene-related environmental factors, atopic disorders, and a randomized introduction of allergenic solids.Methods: A total of 1303 exclusively breast-fed infants were enrolled in a dietary randomized controlled trial (Enquiring About Tolerance study) from 3 months of age. In this nested longitudinal study, fecal samples were collected at baseline, with additional sampling of selected cases and controls at 6 and 12 months to study the evolution of their gut microbiota, using 16S ribosomal RNA gene-targeted amplicon sequencing.Results: In the 288 baseline samples from exclusively breast-fed infant at 3 months, the gut microbiota was highly heterogeneous, forming 3 distinct clusters: Bifidobacterium-rich, Bacteroides-rich, and Escherichia/Shigella-rich. Mode of delivery was the major discriminating factor. Increased Clostridium sensu stricto relative abundance at 3 months was associated with presence of atopic dermatitis on examination at age 3 and 12 months. From the selected cases and controls with longitudinal samples (n = 70), transition to Bacteroides-rich communities and influx of adult-specific microbes were observed during the first year of life. The introduction of allergenic solids promoted a significant increase in Shannon diversity and representation of specific microbes, such as genera belonging to Prevotellaceae and Proteobacteria (eg, Escherichia/Shigella), as compared with infants recommended to exclusively breast-feed.Conclusions: Specific gut microbiota characteristics of samples from 3-month-old breast-fed infants were associated with cesarean birth, and greater Clostridium sensu stricto abundance was associated with atopic dermatitis. The randomized introduction of allergenic solids from age 3 months alongside breast-feeding was associated with differential dynamics of maturation of the gut microbial communities.

KW - Atopic dermatitis

KW - bacteria

KW - colonization

KW - diet

KW - environment

KW - food

KW - microbiome

KW - tolerance

UR - http://www.scopus.com/inward/record.url?scp=85100019727&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2020.09.042

DO - 10.1016/j.jaci.2020.09.042

M3 - Article

C2 - 33551026

AN - SCOPUS:85100019727

SN - 0091-6749

VL - 147

SP - 613-621.e9

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

ER -

Gut microbiota development during infancy: Impact of introducing allergenic foods

Abstract

Keywords

ASJC Scopus subject areas

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Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

Cite this

Gut microbiota development during infancy: Impact of introducing allergenic foods

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

Cite this