Kavli Affiliate: Michael Miller
| Authors: Mikaela C Kasperek, Adriana Velasquez Galeas, Maria Elisa Caetano-Silva, Zifan Xie, Alexander V Ulanov, Michael R La Frano, Suzanne Devkota, Michael J Miller and Jacob M Allen
| Summary:
Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity could be traced to a class of microbial metabolites derived from aromatic amino acids (ArAA), termed aryl-lactates. Using targeted metabolomics, we established that the aryl-lactates phenyllactic acid (PLA), 4-hydroxyphenyllactic acid (4-HPLA), and indole-3-lactic acid (ILA), are present in varying concentrations across a wide range of commercially available fermented foods, including many vegetable and dairy ferments. After pinpointing fermented food-associated lactic acid bacteria (LAB) that produce high levels of aryl-lactates (e.g., Lactiplantibacillus plantarum), we utilized our knowledge of LAB metabolism to identify fermentation conditions (added cultures [e.g., L. plantarum] and metabolic co-factors [e.g., aryl-pyruvates]) to increase aryl-lactate production in food matrices up to 5×103 fold vs. standard fermentation conditions. Next, using ex vivo reporter assays, we found that a variety of food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and/or commercial brands. Moreover, we determined that strategies to enhance aryl-lactates effectively maintained food matrix AhR bioactivity across 4 weeks of storage. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance microbially produced aryl-lactates and thus AhR bioactivity of fermented foods can be leveraged to improve human health.