Gut Microbiota Maturity Mediates the Protective Effect of Siblings on Food Allergy

Children living in larger households are less likely to have allergic disease and asthma, but the underlying mechanisms remain unclear. This study investigated whether the protective effect of older siblings against IgE-mediated food allergy was associated with maturation of the infant gut microbiota.An unselected antenatal sample frame was used to recruit 1074 infants in southeastern Australia.Fecal samples were collected at 1 month, 6 months, and 1 year of age. Fecal 16S rRNA sequence data were obtained for at least 1 of these time points. Microbiota-by-age z scores (MAZ) representing the gut microbiota maturation over the first year of life were calculated using fecal amplicon sequence variants in a random subcohort (n = 323). Skin prick testing and food challenges were done at 1 year of age to determine food allergy status. The authors used a case-cohort design to compare infants with food allergy to the random subcohort of infants.Having a greater number of siblings was associated with a higher MAZ at age 1 year (β = 0.15 per additional sibling; 95% confidence interval, 0.05–0.24; P = .003). A more mature microbiota at age 1 year, but not at age 1 and 6 months, was associated with reduced risk of developing food allergy (odds ratio 0.45; 95% confidence interval, 0.3–0.61; P < .001). MAZ at age 1 year mediated 63% of the protective effects that greater sibling numbers had on food allergy.The protective effect of older siblings on the risk of developing food allergy is in part mediated by advanced maturation of the gut microbiota in late infancy.The hygiene hypothesis has been supported by several studies demonstrating reduced risk of allergic diseases in houses with greater number of siblings and pets. This longitudinal cohort study provides insight on possible mechanisms underlying the protective effects of older siblings on food allergy. The findings highlight the importance of gut microbiome in immune development. Further research may identify potential interventions in late infancy to prevent allergic disease.