Polyphenols, gut health, and longevity: a vital connection

Aging and lifestyle factors

Aging is a process that is very much influenced by lifestyle factors. Habits developed early in life and practiced throughout impact lifespan and health status. Now, a new research article by Beaver et al. highlights the role of two factors that may promote healthy aging: diet and gut microbiota.^[1]

Advances in Nutrition published “Promotion of Healthy Aging Through the Nexus of Gut Microbiota and Dietary Phytochemicals,” an in-depth review of the research on the relationship between phytochemicals, gut health, and aging. Read on as we explore this important topic.

Gut Microbiome Changes - A Hallmark of Aging

Changes in the gut microbiome are recognized as a hallmark of aging. Dysbiosis—an imbalance in the microorganisms in the gut—interacts with other hallmarks and is linked to chronic disease development. Studies suggest that there is a bidirectional relationship between cellular aging and dysbiosis. Physiological changes like slowed motility and a decline in digestive enzyme secretion will contribute to gut microbiome changes, and changes in the microbiome can accelerate cellular aging.^[2]

The gut microbiota plays a crucial role in our health, supporting intestinal barrier function, bolstering immune defenses against harmful pathogens, and aiding in nutrient metabolism. But its influence extends far beyond the gut^[3]. The metabolites it produces—known as postbiotics—circulate throughout the body, acting as signaling molecules that impact various organ systems.

One notable postbiotic is Urolithin A, a compound that activates mitophagy (the process of clearing out damaged mitochondria). Our gut microbiome converts ellagitannins—polyphenols found in foods like pomegranates, berries, and nuts—into Urolithin A, though not everyone’s microbiome has the right bacteria to do so efficiently.

Interestingly, studies of healthy centenarians (those who live past 100 years) reveal that their microbiome closely resembles that of younger individuals, and diet may be a key player here. Studying the microbes in the gut that are associated with health and disease may help predict health with age.

The Role of Diet on Gut Health

Proper diet is one factor that may positively affect gut health. A diet that supports gut health is one that is rich in plant-source foods containing fibers and phytochemicals. Phytochemicals are compounds that may help reduce inflammation and maintain the right balance in the gut. When the bacteria in the gut interact with phytochemicals, microbial metabolites (postbiotics) are produced, which are compounds that also promote health.^[4]

Effects of Phytochemicals on the Gut

Phytochemicals play an important role in maintaining gut health, and one reason for this is their anti-inflammatory effects. Various phytochemicals, such as flavonoids, polyphenols, and tannic acids have been shown to combat inflammation. ^[5]There are different ways these phytochemicals work to do this:

• Phytochemicals work to suppress inflammation by working to inhibit NF-κB, a group of proteins involved in the inflammatory response.^[7] This may protect against chronic inflammation, which has been associated with the development of disease.^[6]
• Certain phytochemicals may also function as prebiotics, compounds that fuel the microbes in our gut.^[8]
• Some research has shown that supplementation with phytochemicals seems to promote beneficial microbes in the gut.^[9]
• There may be even more benefits of phytochemicals when combined with probiotics, which are live bacteria and yeast that have been shown to have positive effects gut health.^[10]

Postbiotics of Interest

Phytochemicals may also contribute to healthspan through the production of microbial metabolites. Foods such as berries, citrus fruits, nuts, some vegetables, and soy contain antioxidants that may promote the production of these metabolites. However, lots of factors, including aging, can influence this production.^[11]

Below is a list of postbiotics highlighted in Beaver et al.’s review:

Urolithins

Urolithins are a class of compounds produced from ellagitannins and ellagic acid, phytochemicals that are found in foods such as pomegranates, berries, and nuts.^[12] Urolithin A (UA) has the most activity in the body and is of interest when it comes to healthy aging.^[13] Research has shown that it may suppress inflammation, promote healthy muscle with age, and protect against bone loss^[14].

Urolithin A works by triggering mitophagy, a critical quality control mechanism that recycles dysfunctional mitochondria, replacing them with healthier, more efficient ones. Clinical trials with Mitopure, a clinically validated Urolithin A supplement, have shown the following benefits:

• Increased cellular energy^[15]
• 12% improvement in muscle strength after 4 months of 500 mg^[16]
• 17% improvement in muscle endurance after 2 months of 1000 mg^[17]

Previous research has shown that only 40% of people have the right microbiome to produce Urolithin A after consuming the necessary phytochemicals from food.^[18]

Hesperetin

Hesperetin is made by bacteria in the intestine from hesperidin, which is an antioxidant compound found in the peel of citrus fruits.^[19] Hesperetin has been found to have beneficial effects on the gut, including reducing inflammation, and it may promote the growth of beneficial bacteria.^[20]

Equol

Equol is phytoestrogen formed by the gut after eating soybeans and other legume. Clinical trials suggest that most humans are unable to produce equol from their microbiome.

Equol is of particular interest because it mimics the effects of estrogen in the body, which may have implications for menopausal health, bone density, and cardiovascular function.^[21] It is also actively being studied for its potential role in cognition and brain health.^[22]

Other Metabolites

The authors mention some of the other microbial metabolites that may promote healthy aging, which include naringenin, baicalein, and capsiate, among others. Studies have shown that these may have many different effects, including the protection of various organ systems and improved skin and bone health.

The authors note that in many of the studies, the metabolites were given in a pure form rather than from food, so more research is needed to see if consuming them naturally in the diet gives the same benefits.^[23]

Moving Forward

This new article highlights how important it is to consider diet and gut health when developing strategies to promote healthy aging. The authors highlight the key role of phytochemicals in maintaining gut health. Microbial metabolites like Urolithin A, which are produced from eating phytochemicals, have been found to have many beneficial effects, such as promoting cellular health and targeting the hallmarks of aging. The authors note that additional studies in diverse groups will allow for a greater understanding of how these microbial metabolites promote health.

The original publication can be found here.