How Specific Bacteria Produce Urolithin A and B for Health and Longevity

The human gut is a complex ecosystem of microorganisms that play vital roles in maintaining and supporting health. Recently, scientists have identified specific bacteria capable of producing urolithins, which are by-products of ellagitannin fermentation.

Urolithins are gaining attention in the scientific community due to their anti-cancer and anti-aging properties. As new research advances, it's becoming possible that the origins of aging may be linked to the gut microbiome.

In this article, we explore a study by Iglesias-Aguirre and colleagues, who identified a new fecal bacterium capable of producing urolithin A and B, and the potential implications for future health interventions.

Understanding Urolithins and Their Connection to the Gut Microbiota

Urolithins are metabolites produced by gut microbes when they ferment specific polyphenols, such as ellagitannins and ellagic acid. These compounds, discovered two decades ago, are celebrated for their health potential.

Ellagitannins (ETs) and ellagic acid (EA) are found in foods such as:

• Pomegranates
• Strawberries
• Raspberries
• Blackberries
• Walnuts
• Tropical fruits
• Herbal teas (green and black Camellia sinensis)

Although ETs and EA are not highly bioavailable, gut microbes can metabolize them into urolithins.

Urolithin Metabotypes

So far, 13 different urolithins have been identified in blood, feces, urine, and various tissues, including the prostate, colon, and breast. The production of urolithins and the associated health benefits of ellagitannins vary between individuals, as not everyone has the gut bacteria required to produce them.

Urolithin metabotypes are categorized into three phenotypes, based on the urolithins individuals can produce:

• UM-A: Produces urolithin A
• UM-B: Produces iso-Uro A and urolithin B
• UM-0: Does not produce Uro-A, iso-Uro-A, or Uro-B

Research indicates that different populations may exhibit varying urolithin metabotypes. For instance, a 2022 study by Anurag et al. found that 12% of participants had circulating urolithin A at baseline, increasing to 40% after consuming pomegranate juice. This suggests that 60% of individuals in the United States may be non-producers. In comparison, studies show that about 10% of individuals on a typical Mediterranean diet in Spain, and 14% of Chinese subjects, exhibit the UM-0 metabotype.

All studies agree that urolithin production is influenced by the gut microbiome composition, and that diet plays a role in shaping this microbial environment. This could explain why populations with high-fiber diets tend to have a greater prevalence of urolithin producers compared to Western dieters.

The Role of Specific Gut Bacteria in Urolithin Production

Advancements have been made in identifying specific bacteria responsible for urolithin production. For example, Gordinobacter species can convert ellagic acid into urolithins and are associated with urolithin A production and the UM-A metabotype. On the other hand, Ellagibacter isourolithinfaciens is linked to iso-Uro-A and UM-B production.

Understanding the role of different bacteria in urolithin production is important because emerging evidence suggests that urolithin metabolites are closely associated with health outcomes. For example, a study by González-Sarrías et al. (2017) found that UM-B individuals had a higher cardiovascular risk. However, after consuming pomegranate extract, their total cholesterol and LDL levels decreased due to increased urolithin production and a rise in Gordinobacter abundance.

How Bacteria Metabolize Ellagic Acid into Urolithin

Iglesias-Aguirre et al. (2023) sought to define the bacteria that contribute to human urolithin metabotypes. While some species are known, many remain unidentified. The researchers isolated bacteria from the fecal sample of a healthy woman who produced urolithins A and B.

They found that the Gordinobacter genus, commonly found in UM-A metabotypes, can metabolize ellagic acid into various intermediates, such as:

• Uro-M5
• Uro-M6
• Uro-C

Another genus, Ellagibacter, can also metabolize these urolithins as well as iso-Uro-A. However, certain bacteria were unable to produce urolithin A from Uro-C or urolithin B from Uro-A, indicating that other unknown bacteria are needed to complete the process.

Discovery of a New Bacterium Producing Urolithins A and B

The study revealed a new bacterium in the feces of a healthy woman that could produce urolithins A and B from Uro-C and iso-Uro-A. This strain, Enterocloster bolteae CEBAS S4A9, was found to have a 99.8% genetic similarity with E. bolteae DSM 15670.

The researchers tested two bacterial mixes to mimic the UM-A and UM-B metabotypes. They found that both mixes, which included E. bolteae CEBAS S4A9, behaved similarly to the natural metabotypes, suggesting that different compositions of gut bacteria impact urolithin production.

Future Practical Applications

The discovery of these urolithin-producing bacteria has significant potential, especially given that the UM-0 prevalence in the U.S. is predicted to be over 60%. These bacteria could be used in probiotic supplements to enable urolithin production in non-producing individuals.

Urolithin A is gaining prominence for its health and anti-aging benefits. Research has shown it can reduce age-related muscle decline, alleviate osteoarthritis symptoms, and improve brain health.

Although more research is needed to determine the safety and efficacy of these bacteria in humans, the potential for their use as next-generation probiotics is exciting.

Summary

Urolithin A has been highlighted for its health benefits, produced by gut microbes from ellagitannin-containing foods. However, not everyone can produce urolithins due to variations in gut microbiome composition. This study identifies pathways and bacterial strains involved in urolithin production, paving the way for future research and potential probiotic applications.

About the Author: Leanne Edermaniger, M.Sc. Leanne is a professional science communicator who specializes in gut microbiome.

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