Isoflavone consumption reduces inflammation through modulation of phenylalanine and lipid metabolism

Introduction: Phytoestrogen found in soy, fruits, peanuts, and other legumes, has been identified as a metabolite capable of providing beneficial effect in multiple pathological conditions due to its ability to mimic endogenous estrogen. Interestingly, the health promoting effect of phytoestrogens such as isoflavone is dependent on the presence of gut bacteria with ability to metabolize dietary phytoestrogen into metabolite such as equol which have higher affinity for endogenous estrogen receptors. We have previously shown that patients with multiple sclerosis (MS), a neuroinflammatory disease lack gut bacteria with the ability to metabolize phytoestrogen. We have validated the importance of phytoestrogen and gut bacteria in disease protection utilizing an animal model of MS. Specifically, we have shown that an isoflavone rich diet can protect from neuroinflammatory diseases and that protection was dependent on the ability of gut bacteria to metabolize isoflavone into equol. Additionally, mice on a diet with isoflavone showed an anti-inflammatory response compared to the mice on a phyto-free diet. However, it is unknown how isoflavone and/or equol mediates its protective effect especially the effect of isoflavone on host metabolomics. Objectives: In this study we utilized untargeted metabolomics to identify the metabolites modulated by the presence of dietary isoflavone. Results: We found that the consumption of isoflavone increases anti-inflammatory monounsaturated fatty acids and beneficial polyunsaturated fatty acids while reducing pro-inflammatory glycerophospholipids, sphingolipids, phenylalanine metabolism, and arachidonic acid derivatives. Conclusion: Isoflavone consumption alters the systemic metabolic landscape through resultant increase in monounsaturated fatty acids and beneficial polyunsaturated fatty acids while reducing proinflammatory metabolites and pathways. This highlights a potential mechanism by which an isoflavone diet modulate immune mediated disease.