Cesarean Section Induces Microbiota-Regulated Immune Disturbances in C57BL/6 Mice

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  • Line Fisker Zachariassen, Univ Copenhagen, University of Copenhagen, Dept Vet Clin & Anim Sci, Fac Med & Hlth Sci
  • ,
  • Lukasz Krych, Univ Copenhagen, University of Copenhagen, Dept Food Sci, Fac Sci
  • ,
  • Sara Hansborg Rasmussen, Univ Copenhagen, University of Copenhagen, Dept Vet Clin & Anim Sci, Fac Med & Hlth Sci
  • ,
  • Dennis Sandris Nielsen, Univ Copenhagen, University of Copenhagen, Dept Food Sci, Fac Sci
  • ,
  • Witold Kot
  • ,
  • Thomas Lindebo Holm, Novo Nordisk, Novo Nordisk, Global Res
  • ,
  • Axel Kornerup Hansen, Univ Copenhagen, University of Copenhagen, Dept Vet Clin & Anim Sci, Fac Med & Hlth Sci
  • ,
  • Camilla Hartmann Friis Hansen, Univ Copenhagen, University of Copenhagen, Dept Vet Clin & Anim Sci, Fac Med & Hlth Sci

Epidemiological studies have shown that children born by cesarean section (CS) are at higher risk of developing chronic inflammatory diseases, and it has been suggested that a skewed gut microbial colonization process early in life and altered priming of the immune system are causative. The aim of this study was to clarify whether impaired regulatory immunity in CS-delivered C57BL/6 mice is dependent on gut microbiota (GM) disturbances. The GM of conventionally bred mice born by CS differed clearly from mice born by vaginal delivery. The proportion of regulatory T cells was reduced in mice born by CS, whereas the invariant NKT (iNKT) cell subset was increased compared with vaginal delivery mice. In addition, regulatory markers (Foxp3, Il10, Ctla4) and macrophage markers (Cd11c, Egr2, Nos2) were downregulated, whereas iNKT markers (Il4, Il15) were upregulated in ileum of CS-delivered mice. The GM of CS-delivered mice was sufficient to transfer the shifts in immunity associated with delivery mode when inoculated into germ-free mice. Feeding a prebiotic diet reestablished gene expression of intestinal immune markers and iNKT cells in CS mice but was not sufficient to restore the level of regulatory T cells. The results support that CS delivery is associated with microbiota-mediated shifts in regulatory immunity and, therefore, provide a basis for future microbiota-directed therapeutics to infants born by CS.

OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind202
Nummer1
Sider (fra-til)142-150
Antal sider9
ISSN0022-1767
DOI
StatusUdgivet - 1 jan. 2019

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