(P04-037-24) Tailoring Microbial Amino Acid Metabolism in Fermented Foods to Enhance Nuclear Receptor Activity and Regulate Experimental Colitis Severity

Objectives: We previously found methods to enhance microbial aromatic metabolism towards increased production of bioactive metabolites within a whole food matrix. Here, we tested the ability of these modified food matrices to activate nuclear receptors- Peroxisome proliferator activated receptor gamma (PPARg) and aryl-hydrocarbon receptor (AhR) ex vivo and dampen colitis severity in dextran sulfate sodium (DSS) treated mice.

Methods: Yogurt (starter culture S. thermophilus, L. bulgaricus) was supplemented with metabolic cofactors. After fermentation and 4wk cold storage, yogurt was analyzed for aryl-lactate (e.g. phenyllactic acid [PLA], indolelactic acid [ILA]) concentrations by LC/MS/MS and nuclear receptor bioactivity using AhR and PPARg reporter cell lines. In a subsequent experiment, C57Bl/6 mice received control yogurt or yogurt conditions optimized for aryl-lactates (n=6/group) for 7ds prior and during 7ds of treatment with 2.5% DSS in drinking water to induce moderate colitis. Colitis severity assessed by colonic shortening, weight loss and pathological indices after 3 ds of recovery from DSS.

Results: Augmented microbial metabolism towards production of aryl-lactates enhanced the ability of fermented foods to activate AhR both immediately post-fermentation and after 4wk cold storage (p < 0.01). Yogurt with standard starter culture exhibited AhR activity similar to commercially available yogurts (p >0.05). We found that food matrix conditions that most robustly augmented the aryl-lactate ILA, also most effectively enhanced AhR activity (p < 0.05). Additionally, preliminary testing revealed food matrices with elevated PLA have capacity to activate PPARg. In light of reduced AhR and PPARg signaling as etiologic factors in inflammatory bowel diseases, we are currently testing whether yogurt optimized for aryl-lactates, including ILA and PLA, can synergize to enhance recovery from an experimental (DSS) colitis challenge.

Conclusions: Increased microbial aryl-lactates enhanced ability of fermented foods to activate AhR. We are leveraging these results to determine if increased AhR and PPARg activity of fermented foods enhance recovery from acute experimental colitis. These data provide insight into bioactive components within fermented foods and reveal methods to enhance aspects of fermentation to improve health.

Funding Sources: USDA NIFA