Abstract

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

Highlights

  • Recent decades have witnessed an increasing prevalence of delivery by cesarean section (CS) across the globe [1]

  • To confirm if delivery mode has an effect on food allergy, we developed a rat food allergy model based on CS

  • Levels of the allergy marker histamine were significantly higher in both tissue and serum of OVAtreated CS rats than those in vaginal delivery (VD) rats, indicating more severe anaphylaxis in CS rats (Figure 1F)

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Summary

Introduction

Recent decades have witnessed an increasing prevalence of delivery by cesarean section (CS) across the globe [1]. CS in mice has been shown to result in marked and long-term behavioral changes, regulatory immunity shifts, and increased sensitivity to oxazolone-induced colitis compared with mice delivered vaginally in offspring [8,9,10,11]. The microbial flora appears to have a significant impact on programming oral tolerance, and the development of Th2 and IgE responses to food antigens is linked to the absence of microbiota in germ-free mice [16, 17]. Fecal transfer from infants with cow’s milk allergy and from mice sensitized by ovalbumin (OVA) induces food allergies in the recipient germ-free mice [18, 19]. Germ-free animals are specialized models, and it is uncertain if more medically relevant changes in the microbiota makeup early in life could have longterm immunological and anaphylactic effects

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