Gut microbial metabolism of peanuts generates immunoregulatory metabolites

Early life introduction of potentially allergenic foods such as peanuts is important for the prevention of food allergy. We hypothesized that peanut consumption may indirectly influence the immune system via effects on gut microbiota composition and metabolism. In vitro human fecal fermentations with peanuts were performed. Changes in taxa and metabolism were measured using 16S rRNA gene sequencing and untargeted metabolomics respectively. Ten Bifidobacterium strains were cultured in vitro in the presence of peanuts and human peripheral blood mononuclear cells (PBMCs) were used to assess culture supernatant immunomodulatory effects. Fecal samples were sequenced from children at 12 months (n = 343) using whole genome metagenomic sequencing. An online questionnaire was used to collect dietary data. Human fecal bioreactor fermentation of peanut flour, previously subjected to in vitro simulated gastrointestinal digestion, resulted in significant production of short-chain fatty acids (SCFA), associated with increased relative abundance of Megasphaera and bifidobacteria. 188 metabolites were significantly altered following peanut fermentation. Bifidobacterium longum subspecies longum strain 160 efficiently metabolized peanut associated with secretion of indole-3-lactic acid (ILA). Following growth on peanuts, bifidobacterial supernatants enhanced IL-10 secretion, but reduced TNF-alpha and IL-5 secretion from stimulated PBMCs. Peanut consumption by 12-month-old children was associated with significant changes in gut microbiota composition including increased levels of Prevotella buccae, Megasphaera micronuciformis and Blautia wexlerae. Peanuts are metabolized by microbes generating immunoregulatory metabolites such as SCFAs and ILA. These metabolites may represent one potential mechanism underlying the allergy-protective effects of early peanut consumption, which requires further validation in high-risk allergy cohorts.