Overcoming Maternal Worries: A Journey to Prevent Infants From Food Allergies by Enhancing Dietary Variety and Boosting Gut Health

Over recent decades, the rising prevalence of food allergies (FA) has promoted investigations into their underlying mechanisms.¹ It has been identified that the complex interaction of genetic, dietary, and environmental factors plays a role in the development of FA.² The key factors presumed to link these elements are diet diversity and the composition of the early life microbiome.³,⁴ The gut microbiome at birth is of low diversity; however, by the ages of 1 to 2 years, its composition becomes similar to that of adults.⁵ This implies the need to cultivate a diverse microbiome during the first year after birth to lower FA risk.⁶ Notably, the significant transition during a child’s first years occurs from 4 to 6 months with the introduction of solid foods. As complementary feeding progresses, the microbial composition changes (increase in the diverse groups of Ruminococcaceae and Lachnospiracea species and decrease of Bifidobacterium, Lactobacillaceae, Enterobacteriaceae, Enterococcaceae and Clostridiaceae) as well as total diversity increase.⁷ Dietary diversity (DD) has been shown to enhance gut microbiome diversity and butyrate production.⁸ The PASTURE study showed that children with the highest butyrate within the first year had a lower risk of FA.⁹ Butyrate plays a role in the development of tolerance through the upregulation of regulatory T cells and reduction of Th2 cytokine production in the gut.¹⁰ Therefore, the timing and diversity of solid foods are pivotal for actively shaping the gut's microbial composition.

The ‘dual allergen hypothesis’ revealed an association between atopic dermatitis and the subsequent development of FA. It proposes that exposure to food allergens through eczematous skin could lead to FA, while oral exposure could lead to tolerance.¹¹ Consequently, prevention studies of FA have focused on preserving the skin barrier and changing the introduction of solid foods during infancy. The infant feeding guidelines for preventing allergy recommended completely avoiding allergenic foods until at least age 1 year.¹² To date, this concept has been revised on the basis of evidence from randomized controlled trials, and delayed introduction of allergenic foods beyond age 4 to 6 months is not necessary.¹³ Although there are heterogeneity and gaps in dietary cultures across the countries, recent guidelines suggest the early introduction of specific allergenic foods (peanuts and eggs, etc.), especially in high-risk groups for allergies.¹⁴,¹⁵,¹⁶ In addition, the European Academy of Allergy and Clinical Immunology task force report, the American Academy of Allergy, Asthma and Immunology, Canadian Society of Allergy and Clinical Immunology and the American College of Allergy, Asthma and Immunology concluded that more diverse diet in infancy may reduce the risk of developing FA in childhood.¹⁴,¹⁷ This represents a significant departure from previous advice and can potentially induce confusion among healthcare professionals and caregivers.¹⁶ This scenario poses a considerable challenge for individuals characterized by anxiety, as it involves moving away from the traditional practices and introducing solid foods to infants earlier than previously believed. During this conceptually transitional phase, intriguing research findings have been documented regarding postpartum maternal anxiety, the timing of introducing solid foods, the subsequent changes in the gut microbiome and the development of FA.

In the current issue of the Allergy, Asthma & Immunology Research, Cho et al. ¹⁸ investigated the influence of postpartum maternal anxiety on DD at monthly intervals between ages 3 to 6 months, the composition of the gut microbiome at 6 months of age, and the incidence of FA over a 2 year follow-up period within a prospective birth cohort. The findings indicated that an increase in maternal anxiety from 2 to 6 months postpartum was correlated with reduced DD at 4 months (estimate = −0.074 [95% confidence interval {CI}, −0.123 to −0.024], P = 0.004). Additionally, decreased DD at 4 months was associated with reduced gut microbial richness at age 6 months (estimate = 0.17 [95% CI, 0.082 to 0.268], P < 0.001). The lower richness, in turn, was significantly related to a higher incidence of FA over a 24-month period (estimate = −0.677 [95% CI, −1.135 to −0.219], P = 0.004). While no direct effect was observed between postpartum maternal anxiety and FA development by age 2, an indirect effect was identified through DD score at 4 months (estimate = 0.009 [95% CI, 0.000 to 0.017], P = 0.042). In this study, lower DD scores and higher maternal anxiety levels before the age of 6 months were associated with increased abundances of Prevotella, Neisseria, Haemophilus, and unclassified Clostridials in their gut microbiome. No significant relationship was found between prenatal maternal anxiety or anxiety level at 2 month and DD, respectively.

The recent research investigating the association between maternal psychological stress and the infant gut microbiome development has concentrated on the prenatal period.¹⁹ Several pathways have been proposed: the transmission of maternal stress responses (e.g., cortisol) to the offspring, which may involve the transplacental passage of neurotransmitters and pro-inflammatory cytokines,²⁰,²¹ or maternal stress-induced alterations in the fetal dendritic cell network that may hinder the induction of peripherally regulatory T cells and Th1/Th17 responses.²² However, in the current study, the authors suggest that the increased postpartum maternal anxiety, particularly from 2 to 6 months of age, may influence the infant’s gut microbiome via the low DD. It was significantly associated with the gut microbiota composition which was related to the development of FA, as explored through mediation analysis. This approach has novel insights into FA prevention. Alleviating maternal anxiety about the introduction of diverse foods—through providing accurate information and guidance to caregivers—could be an effective strategy for FA prevention.

In the study by Cho et al.,¹⁸ the average DD scores at 4 months for the FA and healthy control groups are 1.09 ± 1.10 and 0.85 ± 0.80, respectively. It indicates that the healthy control group often attempts more than one food group at 4 months, whereas the FA group, shows fewer instances of trying foods among the 11 food groups (grains, vegetables, fruits, meat, fish, egg yolks, egg whites, dairy, wheat, peanuts, and legumes/nuts). The French nationwide ELFE cohort showed that late introduction of complementary feeding (> 6 months) was related to FA (odds ratio [OR], 1.35 [95% CI, 1.02 to 1.78]).²³ Moreover, the avoidance of 2 or more allergenic foods until the age of 10 months was linked to an increased likelihood of developing FA (OR, 2.46 [95% CI, 1.77 to 3.42]).²³ For these reasons, if an infant between 4-6 months of age can hold their head up and shows interest in foods commonly consumed by the family, starting solid foods and facilitating exposure to a variety of foods during the later stage of infancy could be beneficial in preventing FA. The American Academy of Pediatrics mentioned recommendations in 2019, stating that it is no longer necessary to wait 3–5 days between introducing each new food.²⁴,²⁵ The core message from the guidelines for the prevention of FA emphasizes that infants should adhere to a healthy and balanced diet, which is usual for the community and family, rather than attempting to prevent FA through the avoidance of specific foods.¹⁵

There are several limitations to this work. Firstly, the sample size of FA patients was limited to fifteen. Secondly, the factors that may influence maternal anxiety during 2- to 6-month period after birth were not explored. Thirdly, environmental factors that can impact the gut microbiome and development of FA, such as prenatal maternal gut microbiome, maternal high-fiber diet, and environmental microbial diversity, were not addressed. Despite some limitations, the study conducted by Cho et al. ¹⁸ implies that it is imperative to investigate RCTs to establish practical guidelines for complementary feeding in infant. These guidelines need to be tailored to accommodate the diverse dietary cultures and varying prevalence of allergenic foods. South Korea, where this study was conducted, is also experiencing a rising trend in FA, making it a timely moment for an expert consensus on weaning guidelines for the prevention FA. The strategies for implementing guidelines for FA prevention also need to be examined for caregivers experiencing anxiety.