Journal of Clinical Immunology and Allergy

Introduction

The incidence of allergic diseases such as asthma, atopic dermatitis, food allergies, and allergic rhinitis has increased dramatically in recent decades, raising concerns about the environmental and biological factors contributing to this trend. While genetic predisposition plays a role, the rapid rise in prevalence cannot be explained by genetics alone, pointing to environmental influences and early-life determinants. Among these, the maternal microbiome and epigenetic imprinting during pregnancy and early childhood have emerged as critical factors shaping immune development and modulating allergy risk in offspring. The maternal microbiome, encompasses the community of microorganisms residing in the gut, skin, oral cavity, and reproductive tract. Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNAs, serve as molecular mediators that translate maternal environmental exposures into long-lasting changes in gene expression without altering the DNA sequence. Together, these factors establish the foundation for immune tolerance or dysregulation, thereby determining susceptibility to allergic diseases. This explores how maternal microbial communities and epigenetic modifications converge to influence childhood allergy risk, highlighting mechanistic insights, clinical evidence, and implications for prevention and intervention [1].

Description

The maternal microbiome exerts a profound influence on the developing immune system of the fetus and neonate, beginning in utero and continuing during birth and breastfeeding. The gut microbiota, in particular, produces metabolites such as short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which cross the placental barrier and interact with fetal immune cells. These metabolites enhance the differentiation and function of regulatory T cells (Tregs), which are critical for establishing immune tolerance to allergens. SCFAs also influence epigenetic processes by inhibiting histone deacetylases, thereby modifying chromatin accessibility and gene expression in fetal immune pathways. Additionally, maternal microbial composition shapes systemic inflammation and metabolic homeostasis, which in turn affects the intrauterine environment [2]. The mode of delivery represents another critical determinant linking the maternal microbiome to childhood allergy risk. Vaginal delivery exposes the neonate to maternal vaginal and gut microbiota, which colonize the infantâ??s gut and establish an early microbial ecosystem conducive to immune tolerance. In contrast, cesarean section bypasses this exposure and instead favors colonization by skin-associated microbes, leading to delayed microbial diversity and altered immune programming. Epidemiological studies consistently show higher rates of asthma, allergic rhinitis, and food allergies in children born by cesarean section compared to those born vaginally. Similarly, breastfeeding further enriches the infant gut with maternal microbes and provides human milk oligosaccharides (HMOs) that act as prebiotics to support beneficial bacteria. Breast milk also transfers maternal antibodies, cytokines, and microRNAs, reinforcing immune regulation during a critical developmental window. Thus, maternal microbial exposures across pregnancy, delivery, and lactation collectively shape the neonatal microbiome and immune system in ways that profoundly impact allergy risk [3,4].

Histone modifications also play a role by influencing chromatin structure and accessibility of transcriptional machinery. Acetylation of histone tails typically promotes gene activation, while deacetylation represses transcription. Maternal microbiome-derived SCFAs act as histone deacetylase inhibitors, promoting acetylation of genes involved in Treg differentiation and anti-inflammatory pathways. This provides a direct mechanistic link between microbial metabolites and epigenetic regulation of immunity. Additionally, non-coding RNAs, particularly microRNAs (miRNAs) present in maternal blood and breast milk, modulate gene expression post-transcriptionally and contribute to immune programming. For example, certain maternal miRNAs have been implicated in regulating epithelial barrier function and cytokine production, both of which are critical in allergic disease pathogenesis. Clinical and epidemiological studies provide strong evidence for the interplay between the maternal microbiome, epigenetics, and childhood allergy outcomes. Cohort studies such as the Canadian Healthy Infant Longitudinal Development (CHILD) study have demonstrated that reduced gut microbial diversity in early infancy, influenced by maternal factors and delivery mode, is associated with higher risk of asthma and atopy [5].

Conclusion

The maternal microbiome and epigenetic imprinting represent fundamental determinants of childhood allergy risk, acting as mediators between environmental exposures and immune development. Maternal microbial communities provide metabolites and microbial signals that shape fetal and neonatal immune tolerance, while epigenetic mechanisms encode these environmental influences into long-term gene expression patterns. Disruptions in these processesâ??through dysbiosis, cesarean delivery, maternal diet, or antibiotic useâ??can increase susceptibility to allergic diseases. Conversely, interventions such as probiotic supplementation, balanced nutrition, and breastfeeding have the potential to promote immune tolerance and reduce allergy risk. Although further research is required to clarify mechanisms and optimize interventions, the convergence of microbiome and epigenetic science offers a powerful framework for understanding and preventing allergic diseases from the earliest stages of life. By targeting maternal health and prenatal exposures, clinicians and researchers may ultimately shift the trajectory of childhood allergy, reducing the burden of disease across generations.

Acknowledgement

None.

Conflict of Interest

None.

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