Food allergy in children may be associated with dysbiosis
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Key takeaways:
- Dysbiosis was the most prominent in children aged 3 years and older with a peanut allergy.
- Children aged younger than 3 years had fewer differences in gut microbiota regardless of food allergy presence.
Gut microbiomes in children with food allergy may differ from those without food allergy, with fewer differences seen in younger children, according to a study published in Annals of Allergy, Asthma and Immunology.
“I started this study in 2014 when I read about experiments where food allergy could be induced or eliminated by fecal microbial transplant in mice,” Punita Ponda, MD, FACAAI, FAAAAI, associate division chief and associate professor of medicine and pediatrics at Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, told Healio.
“Along with this, the observations that societies with similar genetics but different microbiomes had vastly different risks of food allergy, [such as] East and West Germany,” she continued. “Along with this, the observation that young children seemed to handle oral immunotherapy with foods better, led to the interpretations of the data.”
Methods
This real-world prospective cross-sectional study recruited children in two age groups — aged less than 3 years and aged 3 to 18 years — with a confirmed milk, egg or peanut allergy between 2014 and 2019.
The cohorts consisted of one healthy control (HC) group with children without a current or a history of food allergy (FA), atopic dermatitis, allergic rhinitis or asthma and a food allergic group that had a history of FA, a current complete avoidance of the food, and food specific IgE levels or a positive oral food challenge result in the past 6 months.
Each participant provided a baseline stool sample and a caregiver-completed questionnaire that included diet, race, assigned sex at birth, household pets, comorbid conditions, concurrent medications and antibiotic exposure. Caregivers of children aged younger than 3 years also provided information about mode of delivery, breastfeeding and oral antibiotic exposure in the first year of life.
After stool sample analyzation, researchers further divided the FA cohort into persistent and resolving FA groups.
The primary objective of the study was to compare the microbiome of children with FA with children without FA. To do so, researchers evaluated alpha diversity, defined as a measure of the number and relative abundance of taxa within each sample and calculated by the median Shannon diversity index; beta diversity, defined as a measure of similarity between samples, using total-sum scaling; and differential abundance analysis at the phylum, class, order, family and genus levels, for which an absolute fold change [FC] greater than 2 indicated statistical significance.
Secondary analyses included subgroups of milk and/or egg allergy without peanut (MEnoP) allergy, peanut allergy, and persistent vs. resolving MEnoP allergy.
Results
After participant elimination due to adult age, quality checks and batch effects, 70 patients were included in final analysis (FA, n = 56; HC, n = 14).
Alpha diversity appeared lower for any FA compared with the HC group.
Specifically, alpha diversity was lower in older children with FA (2.56; interquartile range [IQR], 2.07-2.98) compared with the HC group (2.85; IQR, 2.47-3.22), whereas children aged younger than 3 years had similar alpha diversity to HCs (2.31; IQR, 2.1-2.58 vs. 2.37; IQR, 2.12-2.72).
Beta diversity was only significantly different by age (P = .001), as children aged younger than 3 years had significantly lower beta diversity.
The researchers also found that 11 a priori taxa at the genus level (Bacteroidetes, Firmicutes and Clostridiales) were differentially abundant in the full cohort regardless of age or FA type (FC = 2-6; P < .05).
Older children in the HC group were significantly differentially abundant in Aestuariispira (FC = 5.3), Gp15 (FC = 2.6), Gp15 (FC = 2.6), Tindallia (FC = 14.71) and Desulfitispora (FC = 2.7) compared with similarly aged patients with FA.
The older group also had a priori differential abundance of family Clostridiaceae_2 (FC = 8.34; P = .032) and Clostridiales_incertae_sedis (FC = 3.12; P = .017).
For children aged younger than 3 years, only a priori taxa including family Clostridiales_Incertae_Se-dis_XIII (FC = 8.15; P = .014) and Clostridiaceae_2_Unknown (FC = 2.86; P = .015) at the genus level were found to be differentially abundant.
Children in the older FA group with a peanut, milk or egg allergy also had significantly lower differential abundance of different taxa compared with the HC group. Acidobacteria_Gp15 at the class level, Acidobacteria_G-p15_Unclassified at the order and family levels and Gp15 at the genus level were all differentially abundant (FC = 2.38-17).
The FA groups also had significantly lower differential abundance of Tindallia at the genus level (FC = 20), and children with peanut allergy were significantly less likely to have Coprococcus genus (FC = 10).
“The finding of Acidobacteria_Gp15 as significant was not expected and should be validated by others,” Ponda emphasized.
Among the 10 children aged younger than 3 years with MEnoP followed for at least 6 months, four had resolved and six had persistent allergies.
Compared with HC group, those with persistent MEnoP had several taxa that were less abundant at the family level whereas in the resolved group, only genus Coprobacillus and Clostridium_sensu_stricto were less abundant.
Conclusions, future studies
Ponda highlighted that the observation of younger patients doing better on oral immunotherapy can be partially supported be these findings.
“It is important to understand how age affects our tolerance to foods,” she said.
She further stated that due to this study, doctors should continue to encourage caregivers to introduce foods early in their children’s diet.
“Waiting after age 3 for introduction to foods may be incorrect since the microbiota would not be as pliable,” she noted. “There should be consideration of pro- and prebiotics in younger children who show atopic diseases or have a high-risk history of atopy. More studies would need to be done about that, though.”
Perspective
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These findings are significant, as they illustrate that dysbiosis is more pronounced in older children, especially those with persistent peanut allergies. This suggests that the timing of exposure to potential allergens and the state of the gut microbiome could play critical roles in the development and persistence of food allergies.
It is somewhat surprising that younger children with food allergies have gut microbiomes similar to those of healthy controls, indicating that early-life microbiome interventions could be particularly effective. This also highlights the fact that gut dysbiosis does get worse over time when interventions to support gut health/improve gut-integrity are not in place.
From a professional standpoint, these findings align with the growing body of evidence suggesting that early intervention and modulation of the gut microbiome could prevent or mitigate the severity of food allergies. The study supports the notion of a “window of opportunity” in early childhood, during which the gut microbiome is particularly malleable and responsive to dietary changes and interventions.
Personally, I have found that my toddler’s food allergy symptoms (in this case to tomatoes) have completely gone away since she has consistently been taking spore-based probiotics to support microbial diversity and improve intestinal barrier function.
Physicians should consider strategies to promote a healthy gut microbiome from an early age as a preventive measure against food allergies. This could include advocating for breastfeeding, timely introduction of potentially allergenic foods according to current guidelines, minimizing unnecessary antibiotic use, encouraging the use of probiotics if antibiotics are needed, and education on prebiotic and probiotic rich food sources.
For older children, especially those with existing food allergies, interventions might need to be more targeted to include treatments such as probiotics or prebiotics to address dysbiosis and potentially additional support to promote improving gut barrier integrity.
Understanding that significant microbiome differences manifest with age, screening and early intervention for food allergies might become a more tailored approach based on individual microbiome assessments. Utilization of stool testing to assess microbial balance could be helpful in knowing which pathogens might be present and/or which beneficial microbes and short-chain fatty acids need to increase to support microbial health.
Future studies should ideally be longitudinal, following children from birth, to better understand how early microbial colonization affects the development of food allergies and how these change with age.
Based on these findings, intervention trials using probiotics or specific dietary changes could be designed to see if altering the gut microbiome can effectively prevent or reduce the severity of food allergies. Including a more diverse demographic could help understand if these findings are universally applicable or if variations exist based on ethnicity, diet or geographic location.
Delving deeper into the mechanisms by which specific microbial changes influence immune responses could pave the way for targeted microbiome therapies in food allergy treatment.
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