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

Imke E Mulder, Bettina Schmidt, Marie Lewis, Margaret Delday, Christopher R Stokes, Mick Bailey, Rustam I Aminov, Bhupinder P Gill, John R Pluske, Claus-Dieter Mayer, Denise Kelly

Research output: Contribution to journalArticle

66 Citations (Scopus)
4 Downloads (Pure)

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.
Original languageEnglish
Article numbere28279
Number of pages10
JournalPloS ONE
Volume6
Issue number12
DOIs
Publication statusPublished - 22 Dec 2011

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Animals
digestive system
Immune system
Chemical activation
Microbiota
intestinal microorganisms
Immune System
animals
Interleukin-23
immune system
T-cells
rearing
Hygiene
microbial colonization
maternal milk
Health Status
adult development
Immunity
Milk
Homeostasis

Cite this

Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. / Mulder, Imke E; Schmidt, Bettina; Lewis, Marie; Delday, Margaret; Stokes, Christopher R; Bailey, Mick; Aminov, Rustam I; Gill, Bhupinder P; Pluske, John R; Mayer, Claus-Dieter; Kelly, Denise.

In: PloS ONE, Vol. 6, No. 12, e28279, 22.12.2011.

Research output: Contribution to journalArticle

Mulder, Imke E ; Schmidt, Bettina ; Lewis, Marie ; Delday, Margaret ; Stokes, Christopher R ; Bailey, Mick ; Aminov, Rustam I ; Gill, Bhupinder P ; Pluske, John R ; Mayer, Claus-Dieter ; Kelly, Denise. / Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. In: PloS ONE. 2011 ; Vol. 6, No. 12.
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AU - Lewis, Marie

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AU - Stokes, Christopher R

AU - Bailey, Mick

AU - Aminov, Rustam I

AU - Gill, Bhupinder P

AU - Pluske, John R

AU - Mayer, Claus-Dieter

AU - Kelly, Denise

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N2 - BackgroundAcquisition 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 FindingsPiglets 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/SignificanceEnvironmental 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.

AB - BackgroundAcquisition 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 FindingsPiglets 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/SignificanceEnvironmental 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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SN - 1932-6203

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