BackgroundAlteration 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.MethodsPublicly 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.ResultsSelf-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.InterpretationAmerican 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.