The Gut "Connections to Health & Disease"

The metabolic effect of gut-derived metabolites coincides with the prevention of conditions like obesity and diabetes in mouse models. However, to produce the beneficial gut-derived metabolites, we need to ingest foods that contain specific bioactive compounds and have beneficial bacterial strains in our gut.

 

Recently, pomegranate polyphenolic compounds and the combination of gut microbiota have been associated with beneficial metabolic effects on mice fed with a high-fat diet. Furthermore, Akkermansia muciniphila, a bacterial strain that resides in the mucosal layer of the gut, is detected in those patients with a healthier metabolic status. Therefore, this connection raises the question does Akkermansia muciniphila improves metabolic homeostasis when combined with pomegranate extract?

Pomegranate extract:

The beneficial effects of pomegranate extract as a prebiotic are attributed to the presence of ellagitannins. Nevertheless, ellagitannins need to be hydrolyzed by the stomach acids and then converted into ellagic acids by the intestinal enzymes. After these processes, the remaining ellagitannins and ellagic acid are metabolized into urolithin by the gut microbiota. 

 

Ellagitannins are not directly absorbed into the bloodstream. On the other hand, the digestive tract where ellagitannins and ellagic acid have more presence and direct interaction with the gut microbiota. Indeed, this interaction also coincides with a beneficial alteration in the gut’s bacteria diversity and the production of urolithin A. 

Akkermansia muciniphila:

This bacterial strain constitutes 3-5% of the microbial community in healthy subjects. Recent studies associate an appropriate abundance of A. muciniphila with healthy body weight and increased muscle mass. Also, in a study where the subjects followed a low caloric diet, this bacterial strain showed consistent abundance. Besides this, several studies associate obesity and type 2 diabetes with less quantity of A. muciniphila.

 

Recent studies have demonstrated an increased proportion of A. muciniphila in mice fed with a high-fat/sucrose diet after drinking cranberry juice. In turn, this increase resulted in reduced weight gain and insulin resistance. Other studies reported significant contributions associated with increased A. muciniphila content; some of them are:

 

• Reversed high-fat diet-induced metabolic disorders.
• Reduced fat-mass gain.
• Less adipose tissue-induced inflammation.
• Increased insulin sensitivity.
• Metabolic endotoxemia prevention.

 Does A. muciniphila metabolize ellagitannin to urolithin A?

Urolithin has multiple isomers; within them, urolithin A associates with numerous health benefits. An increase in this polyphenol gut-derived metabolite coincides with an attenuation of inflammatory signaling, anti-cancer effects, modulation of energetic homeostasis, and anti-aging, specifically to those mechanisms linked to mitochondrial and muscular dysfunction. Furthermore, in animal models, urolithin A increases mitophagy of dysfunctional mitochondria, followed by autophagosome formation, clearing mitochondrial protein. This mechanism improves the quality of cellular mitochondria and promotes the generation of new organelles.

 

However, some studies report that only 40% of people can produce meaningful amounts of urolithin A from its dietary precursors. In turn, this mechanism links to the gut microbiota diversity and A. muciniphila composition.

Clinical findings:

A small study with 18 volunteers measured the effects of 4- week intervention of pomegranate extract, the abundance of Akkermansia muciniphila, and urolithin A production.

This study concluded that those subjects with higher urolithin A production coincide with elevated A. muciniphila in their stools. On the other hand, those urolithin A-non producers had higher levels of ellagic acid in their stool samples after a 4- week intervention with pomegranate extract.

 

There is no doubt about the influence that gut microbiota has on metabolic health. Also, we know all about the extraordinary benefits that polyphenolic compounds provide by modulating inflammatory responses, promoting antioxidant effects, and how they stimulate the growth of beneficial bacteria. However, the apparent interaction between urolithin A production by A. municiphila merges this mechanism and provides additional effects. Furthermore, this interaction promotes mitophagy, resulting in a better mitochondrial function that equates to better energy production (ATP), joint and muscle tissue promotion, and overall health. – Ana Paola Rodríguez Arciniega

 

References:

Henning, Susanne M et al. “Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo.” Anaerobe vol. 43 (2017): 56-60. doi:10.1016/j.anaerobe.2016.12.003

 

D’Amico, Davide et al. “Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.” Trends in molecular medicine vol. 27,7 (2021): 687-699. doi:10.1016/j.molmed.2021.04.009