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

Area of Science:

• Immunology
• Microbiology
• Developmental Biology

Background:

• Cesarean section (CS) delivery is linked to increased chronic inflammatory diseases in children.
• Early-life gut microbial colonization and immune system priming are implicated in CS-associated risks.

Purpose of the Study:

• To investigate if impaired regulatory immunity in mice born via CS is mediated by gut microbiota (GM) disturbances.
• To understand the impact of CS delivery on immune cell populations and gene expression in the gut.

Main Methods:

• Comparison of gut microbiota and immune cell profiles between conventionally bred mice born by CS and vaginal delivery.
• Analysis of regulatory and macrophage markers in the ileum of CS-delivered mice.
• Gnotobiotic mouse model to assess the transferability of CS-associated immune shifts via GM inoculation.
• Intervention study using a prebiotic diet in CS-delivered mice.

Main Results:

• Significant differences in GM composition were observed between CS and vaginal delivery mice.
• CS-delivered mice showed reduced regulatory T cells and increased invariant NKT (iNKT) cells.
• Downregulation of regulatory and macrophage markers, and upregulation of iNKT markers were noted in the ileum of CS mice.
• Inoculation of germ-free mice with GM from CS-delivered mice transferred immune shifts.
• Prebiotic feeding partially normalized immune gene expression and iNKT cells but not regulatory T cells.

Conclusions:

• CS delivery induces microbiota-dependent alterations in regulatory immunity.
• These findings support the development of microbiota-directed therapeutics for infants born by CS.
• Targeting gut microbiota may offer a strategy to mitigate immune dysregulation associated with CS delivery.