Ron Goldberg
In infants with older siblings, advanced maturation of gut microbiota at 1 year of age significantly mediates the risk of developing immunoglobulin E (IgE)-mediated food allergy during infancy, according to study findings published in The Journal of Allergy and Clinical Immunology.
Having siblings and household pets, particularly dogs, seems to have a protective effect on allergic disease, but the reasons behind this are unclear. Investigators sought to determine whether having older siblings accelerated the maturation of gut microbiota in infants, thereby decreasing an infant’s risk of developing IgE-mediated food allergy.
The investigators used data from the Barwon Infant Study in Southeastern Australia, a birth cohort study, from which a subcohort of children who completed the 1-year review (n=323; 45.5% girls) was randomly chosen (38% with 0 siblings; 40%, 1 sibling; 19%, 2 siblings; 4%, 3 or more siblings; 54% with a pet dog).
The current study examined food allergy status assessed at 1 year by in-hospital food challenge and skin prick test. Fecal samples were collected at 1 month, 6 months, and 1 year. The researchers used fecal amplicon sequence variants (ASVs) representing gut microbiota maturation over the first year of life to calculate microbiota-by-age z-scores (MAZ) at each time point. ASVs were derived using 16S rRNA gene amplicon sequencing.
Between-group similarity existed for delivery mode, breast feeding vs formula, age at introduction of solid foods, and age at introduction of the most common food allergen in the cohort (egg).
Investigators found higher MAZ in infants at 1 year of age was associated with a greater number of siblings (b =0.15 per an additional sibling; 95% CI, 0.05-0.24; P =.003). The investigators noted 63% of this protective effect of a greater number of siblings was mediated by advanced maturation of gut microbiota at 1 year of age. This association related to decreased odds of food allergy (odds ratio, 0.45; 95% CI, 0.33-0.61; P <.001), meaning at 1 year of age, decreased odds of clinically proven IgE-mediated food allergy is associated with advanced maturation of infant gut microbiota. This association did not exist at 1 month or 6 months.
Investigators noted no difference in abundance of the 25 most important ASVs at 1 year between infants with and without food allergy. A higher MAZ was associated with having a dog in the home at 1 year of age (b =0.19; 95% CI, 0.02-0.35; P =.03).
Investigators found infants with food allergy had fewer older siblings and were less likely to have a dog in their household. Less mature infant gut microbiota was associated with longer duration of breastfeeding at 1 month (b = -1.10; 95% CI, -1.54 to -0.67; P <.001) and at 6 months, but not at 1 year of age (b = -0.15; 95% CI, -0.38 to 0.07; P =.17).
Study limitations include lack of validated measure of food frequencies and the possibility of reverse causation.
“The protective effect of older siblings on the risk of developing IgE-mediated food allergy during infancy is substantially mediated by advanced maturation of the gut microbiota at 1 year of age,” investigators concluded. “In this Australian birth cohort, delayed maturation of the infant gut microbiota at 1 year of age was associated with an increased risk of clinically proven IgE-mediated food allergy at 1 year of age,” they added.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
The findings described in this study are the subject of a provisional patent, licensed to Prevatex Pty Ltd.
References:
Gao Y, Stokholm J, O’Hely M, et al.; BIS Investigator Group. Gut microbiota maturity mediates the protective effect of siblings on food allergy. J Allergy Clin Immunol. Published online May 5, 2023. doi: 10.1016/j.jaci.2023.02.034