Cinnamic acid

Cleveland Clinic researchers have identified a molecule in elderberry extract and other fruits that may counteract the negative effects of a high-fat diet by slowing weight gain, improving fatty liver disease and reversing insulin resistance. The Molecular Metabolism study explains that these benefits come from our gut bacteria, which digest the molecule into smaller molecules that help regulate metabolism. These findings are a step forward for developing strategies that use the gut microbiome to treat disease and maintain health, guiding dietary recommendations and prebiotic or probiotic therapies. Senior author Jan Claesen, PhD, didn’t set out to study elderberries over any other fruit or vegetable when he started his lab. Study first author Sara Alqudah, a PhD student in his lab, wanted to know how our gut microbiomes help us digest antioxidants called polyphenols. Polyphenols are mostly found in colorful fruits and vegetables, especially berries. We can’t break the molecules down on our own, so the bacteria in our intestines digest polyphenols for us. In preclinical models, the Claesen Lab found that a common gut bacteria called Clostridium sporogenes turns a polyphenol in elderberries (cinnamic acid) into the metabolite 3-phenylpropionic acid (3-PPA). This metabolite travels from the intestines to the liver, where it activates pathways that improve insulin control and reduce fat creation. Directly adding 3-PPA to liver cells in petri dish experiments showed the same results. “We used elderberries for this study because they’re excellent sources of edible polyphenols, not because we think they’re magical,” Dr. Claesen says. “What this study does is showcase some fascinating microbial chemistry that we are now working to understand so we can make interventions that improve our metabolic health. Similar polyphenol compounds are found across plant-based foods, and our gut microbiota can metabolize these into related compounds that might match the potency of 3-PPA." When designed well, drugs that target gut bacteria can improve health without harming human cells. Dietary changes may be even more powerful, because they can positively influence our own cells in addition to our microbes. Dr. Claesen and his team are now working to understand more about how 3-PPA improves our metabolic health, and how we can develop 3-PPA based treatments through methods including: Dietary changes, like incorporating berry-based supplements Prebiotic and probiotic therapies that help Clostridium sporogenes and other cinnamic acid-processing bacteria thrive in our digestive tracts Drug development to deliver pure 3-PPA into our systems While his lab works to turn their preclinical findings into human treatments, Dr. Claesen stresses that he currently does not recommend any specific probiotic, supplement or elderberry product. He also cautions against eating too many raw elderberries due to the risk of cyanide in unripe berries. “Dietary intervention studies are challenging in humans because they require large numbers of participants and long timelines, and funding is a big hurdle,” he says. “My recommendation for now would be to work with your physician on a plan that helps you prevent or manage metabolic diseases, including incorporating colorful fruits and vegetables, and let your microbiome do the rest."