Hansen, Camilla Hartmann Friis6; Andersen, Line Sidsel Fisker6; Krych, Lukasz7; Metzdorff, Stine Broeng6; Hasselby, Jane Preuss8; Skov, Søren6; Nielsen, Dennis Sandris7; Buschard, Karsten5; Hansen, Lars H.9; Hansen, Axel Kornerup6
1 Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet2 Microbiology and Fermentation, Department of Food Science, Faculty of Science, Københavns Universitet3 Microbiology, Department of Biology, Faculty of Science, Københavns Universitet4 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Bartholin Institute, Rigshospitalet6 Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet7 Microbiology and Fermentation, Department of Food Science, Faculty of Science, Københavns Universitet8 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet9 Microbiology, Department of Biology, Faculty of Science, Københavns Universitet
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.
Journal of Immunology, 2014, Vol 193, Issue 3, p. 1213-1222