Gut microbial metabolism of peanuts generates immunoregulatory metabolites

Background. Complementary feeding practices and timing are thought to significantly influence early life immune development, with the early introduction of allergenic foods being especially important for prevention of food allergy. We hypothesized that allergen-containing foods such as peanut, tree nuts and sesame may indirectly influence the immune system via their effects on gut microbiota composition and metabolism. Methods. 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. In vitro human fecal fermentations with peanuts were performed in bioreactors. Changes in taxa and metabolism were measured using 16S rRNA gene sequencing and untargeted metabolomics respectively. A panel of 7 Bifidobacterium longum strains and 3 B. pseudocatenulatum 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. Results. Peanut consumption by 12-month-old children was associated with significant changes in gut microbiota composition and metabolism including increased levels of Ruminococcus bromii , Megasphaera micronuciformis , Blautia wexlerae and enrichment of genes supporting short-chain fatty acid (SCFA) production. The addition of peanut flour or pre-digested peanuts to human fecal bioreactors increased levels of megasphaera, clostridia and bifidobacteria, associated with high levels of SCFA production. 246 metabolites were significantly altered following peanut fermentation. All 10 tested bifidobacterial strains were able to metabolize peanut in vitro , with B. longum strain 160 being the most effective. Following growth on peanuts, bifidobacterial supernatants enhanced IL-10 secretion, but reduced TNF-alpha and IL-5 secretion from stimulated PBMCs. Conclusions. Peanuts are metabolized by early life microbes generating immunoregulatory metabolites. These metabolites may play an important role in their allergy protective effects complementing mechanisms associated with direct antigen sampling by the immune system.