Targeting the Microbiota Reverses C-Section-Induced Effects on Intestinal Permeability, Microbiota Composition, and Amygdala Gene Expression in the Mouse

Background: The microbiome significantly influences the development of the gastrointestinal and immune systems. The delivery method, whether Caesarean section (CS) or vaginal birth (VB), plays a crucial role in shaping microbiota composition, with CS babies exhibiting differences. Early-life nutritional interventions using probiotics or prebiotics may help restore this imbalance in CS infants. Our study aimed to assess gut permeability in CS mice compared to VB mice and explore whether prebiotics or probiotics could mitigate any deficiencies. Methods: Using a mouse model (NIH Swiss) for CS delivery, we measured plasma levels of a 4 kDa macromolecule (FITC) at PND7, 14, 23, and 35. We evaluated ileal gene expression of tight junction proteins, profiled intestinal microbiome composition, and examined the expression of genes involved in neurotransmitter physiology in the amygdala. Additionally, we studied the impact of administering Bifidobacterium breve in drinking water and dietary administration of GOS/FOS on these outcomes. Key Results: At PND7, CS-born mice exhibited increased ileal permeability, along with reduced expression of Tjp1, Occludin, Claudin 3, and Epcam compared to VB mice. Administration of B. breve or GOS/FOS alleviated changes in Epcam expression. During the pre-weaning period, beta diversity differed between VB and CS. Post-weaning, β-diversity increased following probiotic and prebiotic intervention. Additionally, CS mice showed changes in neurotransmitter gene expression in the amygdala, which were also mitigated by B. breve or GOS/FOS. Discussion: Our findings indicate that targeted microbiota-associated interventions can reverse deficits in intestinal permeability induced in CS mice.