Mode of delivery shapes gut colonization pattern and modulates regulatory immunity in mice
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Mode of delivery shapes gut colonization pattern and modulates regulatory immunity in mice. / Hansen, Camilla Hartmann Friis; Andersen, Line Sidsel Fisker; Krych, Lukasz; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Skov, Søren; Nielsen, Dennis Sandris; Buschard, Karsten; Hansen, Lars H.; Hansen, Axel Kornerup.
In: Journal of Immunology, Vol. 193, No. 3, 2014, p. 1213-1222.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mode of delivery shapes gut colonization pattern and modulates regulatory immunity in mice
AU - Hansen, Camilla Hartmann Friis
AU - Andersen, Line Sidsel Fisker
AU - Krych, Lukasz
AU - Metzdorff, Stine Broeng
AU - Hasselby, Jane Preuss
AU - Skov, Søren
AU - Nielsen, Dennis Sandris
AU - Buschard, Karsten
AU - Hansen, Lars H.
AU - Hansen, Axel Kornerup
N1 - Copyright © 2014 by The American Association of Immunologists, Inc.
PY - 2014
Y1 - 2014
N2 - Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section-born mice had lower proportions of Foxp3(+) regulatory T cells, tolerogenic CD103(+) dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.
AB - Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section-born mice had lower proportions of Foxp3(+) regulatory T cells, tolerogenic CD103(+) dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.
KW - Adaptive Immunity
KW - Animals
KW - Bacteroides
KW - Cesarean Section
KW - Clostridium
KW - Diabetes Mellitus, Experimental
KW - Female
KW - Intestines
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Inbred NOD
KW - Microbiota
KW - Mucous Membrane
KW - Ruminococcus
KW - T-Lymphocytes, Regulatory
U2 - 10.4049/jimmunol.1400085
DO - 10.4049/jimmunol.1400085
M3 - Journal article
C2 - 24951818
VL - 193
SP - 1213
EP - 1222
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -
ID: 124556790