Multiscale Study of the Oral and Gut Environments in Children with High- and Low-threshold Peanut Allergy

Background: The oral and gut microbiomes have each been associated with food allergy status. Within food allergy, they may also influence reaction thresholds.

Objective: Our aim was to identify oral and gut microbiota associated with reaction thresholds in peanut allergy.

Methods: A total of 59 children aged 4 to 14 years with suspected peanut allergy underwent double-blind, placebo-controlled food challenge to peanut. Those children who reacted at the 300-mg or higher dose of peanut were classified as high-threshold (HT), those who reacted to lower doses were classified as low-threshold (LT), and those children who did not react were classified as not peanut allergic (NPA). Saliva and stool samples collected before challenge underwent DNA isolation followed by 16S rRNA sequencing and short-chain fatty acid measurement.

Results: The 59 participants included 38 HT children and 13 LT children. Saliva microbiome α-diversity (Shannon index) was higher in LT children (P = .017). We identified saliva and stool microbiota that distinguished HT children from LT children, including oral Veillonella nakazawae (amplicon sequence variant 1979), which was more abundant in the HT group than in the LT group (false discovery rate [FDR] = 0.025), and gut Bacteroides thetaiotaomicron (amplicon sequence variant 6829), which was less abundant in HT children than in LT children (FDR = 0.039). Comparison with NPA children revealed consistent ordinal trends between these discriminating species and reaction thresholds. Importantly, many of these threshold-associated species were also correlated with short-chain fatty acid levels at the respective body sites, including between oral V nakazawae and oral butyrate (r = 0.57; FDR = 0.049).

Conclusion: Findings from this multiscale study raise the possibility of microbial therapeutics to increase reaction thresholds in children with food allergy.