Multi-dimensional study of the oral microbiome, metabolite, and immunologic environment in peanut allergy.

Abstract

BACKGROUND\nThe oral mucosa is the initial interface between food antigens, microbiota and mucosal immunity, yet little is known about oral host-environment dynamics in food allergy.\n\n\nOBJECTIVE\nTo determine oral microbial, metabolic, and immunologic profiles associated with peanut allergy.\n\n\nMETHODS\nWe recruited 105 subjects (peanut allergic n=56, healthy subjects n=49) for salivary microbiome profiling using 16S rRNA sequencing, short chain fatty acid (SCFA) metabolite assays using liquid chromatography/mass spectrometry, and measurement of oral secreted cytokines using multiplex assays. Analyses within and across data types were performed.\n\n\nRESULTS\nThe oral microbiome of peanut-allergic individuals was characterized by reduced species in Lactobacillales, Bacteroidales (Prevotella), and Bacillales, and increased Neisseriales spp. The distinct oral microbiome of peanut-allergic subjects was accompanied by significant reductions of oral SCFA levels, including acetate, butyrate, and propionate, and significant elevation of IL-4 secretion. Decreased abundances of oral Prevotella spp. and Veillonella spp. in peanut-allergic subjects were significantly correlated with reduced oral SCFA levels (FDR<0.05), and increased oral Neisseria spp. was correlated with lower oral SCFA levels (FDR<0.05). Additionally, oral Prevotella spp. abundances were correlated with decreased local secretion of Th2-stimulating epithelial factors (IL-33, TSLP) and Th2 cytokines (IL-4, IL-5, IL-13), while oral Neisseria spp. abundance was positively associated with a Th2-skewed oral immune milieu.\n\n\nCONCLUSION\nOur novel multi-dimensional analysis of the oral environment revealed distinct microbial and metabolic profiles associated with mucosal immune disturbances in peanut-allergy. Our findings highlight the oral environment as an anatomical site of interest to examine host-microbiome dynamics in food allergy.