Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project

Abstract

Background: Alteration of the gut microbial population (dysbiosis) may increase the risk for allergies and other conditions. This study sought to clarify the relationship of dysbiosis with allergies in adults.

Methods: Publicly available American Gut Project questionnaire and fecal 16S rRNA sequence data were analyzed. Fecal microbiota richness (number of observed species) and composition (UniFrac) were used to compare adults with versus without allergy to foods (peanuts, tree nuts, shellfish, other) and non-foods (drug, bee sting, dander, asthma, seasonal, eczema). Logistic and Poisson regression models adjusted for potential confounders. Odds ratios and 95% confidence intervals (CI) were calculated for lowest vs highest richness tertile. Taxonomy associations considered 122 non-redundant taxa (of 2379 total taxa) with ≥ 0.1% mean abundance.

Results: Self-reported allergy prevalence among the 1879 participants (mean age, 45.5 years; 46.9% male) was 81.5%, ranging from 2.5% for peanuts to 40.5% for seasonal. Fecal microbiota richness was markedly lower with total allergies (P = 10(-9)) and five particular allergies (P ≤ 10(-4)). Richness odds ratios were 1.7 (CI 1.3-2.2) with seasonal, 1.8 (CI 1.3-2.5) with drug, and 7.8 (CI 2.3-26.5) with peanut allergy. These allergic participants also had markedly altered microbial community composition (unweighted UniFrac, P = 10(-4) to 10(-7)). Total food and non-food allergies were significantly associated with 7 and 9 altered taxa, respectively. The dysbiosis was most marked with nut and seasonal allergies, driven by higher Bacteroidales and reduced Clostridiales taxa.

Interpretation: American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gut microbiota. This dysbiosis might be targeted to improve treatment or prevention of allergy.

Keywords: 16S rRNA, 16S ribosomal RNA; AGP, American Gut Project; Adults; Allergy; FDR, false discovery rate; Feces; Human microbiome; Hygiene hypothesis; MiRKAT, Microbiome Regression-based Kernel Association Test; NHANES, National Health And Examination Survey; PCoA, principal coordinate analysis; PD, phylogenetic diversity; QIIME, Quantitative Insights Into Microbial Ecology; RA, relative abundance.

Fig. 1

Associations between richness (observed species), alpha diversity and allergies. Upper panel: Association P-values were derived by unconditional logistic regression (for each individual allergy) or by negative binomial regressions (for total allergies), adjusting for age, sex, body mass index (BMI), time since last antibiotics, season, probiotic and vitamin usage. Lower panels: Box plots for the associations of richness (observed_species). Box plots for Shannon index, Chao1 and PD_whole_tree are reported in Fig. E1. In each box plot, “0” and “1” represent the group without and with the specified allergy, respectively.

Fig. 2

Association between microbiome composition (beta diversity) and allergies. Upper panels: Association P-values were calculated by MiRKAT (Zhao et al., 2015) using unweighted and weighted UniFrac distance matrices. Associations were adjusted for age, sex, BMI, time since last antibiotics, season, probiotic and vitamin usage. Lower panels: Box plots of the top PCoA scores based on unweighted UniFrac distance matrix. P-values were based on logistic regression for each individual allergy and by negative binomial regressions for total allergies. Box plots for PCoA2 and PCoA3 are reported in Fig. E2. The top three PCoA scores explained 17.5%, 4.4% and 3.2% of the variance.

Fig. 3

Taxa associated with multiple allergy traits. We identified 13 taxa [false discovery rate (FDR) < 10%] associated with multiple food or non-food allergies. Each taxon's shorthand name, average relative abundance (RA), and a P-value for testing multiple allergy traits based on 100,000 permutations are presented. The heat map shows statistically significant, covariate-adjusted P-values (red for positive, blue for negative) for associations with total allergies (by negative binomial models) and with each allergy (by logistic regression). The Z-scores and P-values for individual taxon associations are in Table E5.