Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

I.E. Mulder; B. Schmidt; M. Lewis; M. Delday; C.R. Stokes; M. Bailey; R.I. Aminov; B.P. Gill; J.R. Pluske; C-D. Mayer; D. Kelly

doi:10.1371/journal.pone.0028279

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Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Journal article

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Peer reviewed

Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

I.E. Mulder, B. Schmidt, M. Lewis, M. Delday, C.R. Stokes, M. Bailey, R.I. Aminov, B.P. Gill, J.R. Pluske, C-D. Mayer, …

PLoS ONE, Vol.6(12), e28279

2011

DOI: https://doi.org/10.1371/journal.pone.0028279

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Abstract

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolator-reared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

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Title: Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity
Authors/Creators: I.E. Mulder (Author/Creator) - University of Aberdeen
B. Schmidt (Author/Creator) - University of Aberdeen
M. Lewis (Author/Creator) - University of Bristol
M. Delday (Author/Creator) - University of Aberdeen
C.R. Stokes (Author/Creator) - University of Bristol
M. Bailey (Author/Creator) - University of Bristol
R.I. Aminov (Author/Creator) - University of Aberdeen
B.P. Gill (Author/Creator) - Agriculture and Horticulture Development Board
J.R. Pluske (Author/Creator) - Murdoch University
C-D. Mayer (Author/Creator) - Rowett Research Institute
D. Kelly (Author/Creator) - University of Aberdeen
Publication Details: PLoS ONE, Vol.6(12), e28279
Publisher: Public Library of Science
Identifiers: 991005544000707891
Copyright: © 2011 Mulder et al.
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article
Note: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.120 Inflammatory Bowel Diseases & Infections; 1.120.384 Gut Microbiota
Web Of Science research areas: Immunology
ESI research areas: Immunology