How to Make Urolithin Postbiotics from Tannins

The short-chain fatty acid called butyrate is the most studied postbiotic, but acetic acid, the defining constituent of vinegar, is another beneficial bug byproduct. When we eat whole plant foods, our gut flora can make acetic acid from scratch in our colons by fermenting the fiber. The acetic acid can then get absorbed back into our bloodstreams, so we can use the top-down approach to activate the anti-aging enzyme AMPK by consuming vinegar, or the bottoms-up approach by eating fiber.

Just as the benefits of fiber result from both the prebiotic fueling of good bacteria and the resulting postbiotic metabolites (the short chain fatty acids), polyphenols can act as both prebiotics and result in beneficial postbiotics. To investigate the mystery of polyphenol action at such low apparent bioavailability, researchers radioactively tagged blueberry anthocyanins to trace them throughout the body. They discovered that the parent polyphenols in the berries are metabolized not only by our liver but also by our microbiome into active metabolites that then circulate throughout our system. There is an immediate bump of blueberry pigments in our blood within an hour of consumption, but a day later new blueberry-derived compounds continue to appear in our bloodstream as our bacteria churn out new goodies from them. Next-day metabolites were also found after eating strawberries. Berry polyphenols can be the gift that keeps on giving.

Dozens of anthocyanin metabolites have been quantified after blueberry consumption, some of which are more powerful than the parent compounds. Expose human artery lining cells to the levels of the anthocyanin metabolites found in the bloodstream after consuming blueberriesand you can ameliorate more damage that occurs after dripping on some saturated fat than if you had exposed the cells to just the anthocyanins themselves at consumption levels. This suggests that extracting the full benefits of berries is a team effort. This explains why antibiotics can blunt the metabolic benefits of blueberries for mice fed a high fat diet.

Postbiotics are defined as beneficial byproducts of microbiome metabolism, such as short-chain fatty acids, the active polyphenol metabolites, or the equol from soy I’ve talked about previously. One class of postbiotics important to aging are urolithins, which are created in our large intestine by our friendly flora from ellagic acid, which is formed in our small intestine when we eat ellagitannins. Elligatannins are the most common form of tannin, characteristically astringent tasting natural compounds found in many of our ancestral foods, including berries, nuts, acorns, and tree leaves. Since tannins aren’t bioavailable, they have been neglected in the field of nutrition, or even considered “antinutrients,” a view that has “changed dramatically” once it was recognized they could be metabolized by our microbiome into urolithins, now thought responsible for some of the benefits of berries, nuts, and pomegranates. For example, significant improvements in artery function within hours of eating about one and a half cups of blended frozen raspberries compared to a fiber-matched control were correlated with circulating levels of urolithins.

In C. elegans urolithins extend lifespan by inducing mitophagy, mitochondria autophagy, which is the prevention of the accumulation of dysfunctional mitochondria with age. A decline in mitophagy has been linked to low muscle mass and poor physical function (slower walking speed) in the elderly. Urolithins have been found to counter age related muscle function decline by improving the exercise capacity of older rats and mice. What about in people? The first human trial was published in 2019 and showed that weeks of urolithin supplementation induced a molecular signature of improved mitochondrial health and biogenesis in muscle biopsies, similar to what one might see after an aerobic exercise regimen. Clinical effects were then demonstrated in 2022.

A randomized double-blind placebo controlled trial of months of urolithin supplementation in adults aged 65 to 90 found that while walking speed was not affected, muscle endurance in both the hand and leg were improved compared to placebo in the absence of any exercise training, suggesting urolithins may help prevent age-related muscle decline. Like any postbiotic, though, it depends on having the requisite microbial machinery. Studies show that some people are poor urolithin producers and other people’s microbiomes can’t make it at all.

Give people a pomegranate extract and producers of urolithins experienced a significant reduction in LDL cholesterol, but the non-producers did not. After a few weeks of supplementation, though, there were a few conversions—non-producers turned into producers. This may explain why vegetarians tend to have a higher abundance of urothin producing microbes, their greater intake of plants. However, some plants have more than others. Among fruits and nuts, high levels of elligitannins have been found in a variety of berries, pomegranates, and walnuts.