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Gut microbiota development during infancy: Impact of introducing allergenic foods - 04/02/21

Doi : 10.1016/j.jaci.2020.09.042 
Tom Marrs, PhD a, b, , Jay-Hyun Jo, PhD c, , Michael R. Perkin, PhD d, Damian W. Rivett, PhD e, Adam A. Witney, PhD f, Kenneth D. Bruce, PhD g, Kirsty Logan, PhD a, Joanna Craven, MPH a, Suzana Radulovic, MD a, b, Serge A. Versteeg, BSc h, Ronald van Ree, PhD h, i, W. H. Irwin McLean, FRS j, David P. Strachan, MD d, Gideon Lack, MD a, Heidi H. Kong, MD, MHSc c, , Carsten Flohr, PhD k, ,
a Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom 
b Children’s Allergies Department, Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, Lambeth, United Kingdom 
c Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md 
d Population Health Research Institute, St George’s, University of London, London, United Kingdom 
e Department of Natural Sciences, Manchester Metropolitan University, Manchester, United Kingdom 
f Institute for Infection and Immunity, St George’s, University of London, London, United Kingdom 
g Molecular Microbiology Research Laboratory, Pharmaceutical Science Division, King’s College London, London, United Kingdom 
h Experimental Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands 
i Department of Otorhinolaryngology, Amsterdam University Medical Center, Amsterdam, The Netherlands 
j Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom 
k Unit for Population-Based Dermatology Research, St John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London, London, United Kingdom 

Corresponding author: Carsten Flohr, PhD, Unit for Population-Based Dermatology Research, St John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, UK.Unit for Population-Based Dermatology ResearchSt John’s Institute of DermatologySchool of Basic and Medical BiosciencesKing’s College London and Guy’s and St Thomas’ NHS Foundation TrustLondonUK

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.

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Graphical abstract




Il testo completo di questo articolo è disponibile in PDF.

Key words : Atopic dermatitis, bacteria, diet, environment, food, microbiome, colonization, tolerance

Abbreviations used : AD, EAT, MA, PCoA, TEDDY


Mappa


 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.
 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.


© 2020  The Authors. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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