Home Gut Microbial Metabolites of Dietary Polyphenols and Their Skin Health Benefits

Gut Microbial Metabolites of Dietary Polyphenols and Their Skin Health Benefits

by james.runkle@drummondst.com

Gut Microbial Metabolites of Dietary Polyphenols and Their Skin Health Benefits

Author:
Hang Ma, Ph.D.
Research Unit for Nutraceutical and Cosmeceutical Applications (RUNCA), Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island

Imagine your gastrointestinal tract as a sophisticated biochemical laboratory, where the vast community of gut microbes metabolizes polyphenols— plant-derived compounds widely found in fruits, vegetables, coffees, and teas. Through complex enzymatic processes, these microbes break down polyphenols into a variety of smaller, bioactive compounds known as polyphenol microbial metabolites (PMMs). These metabolites are important to overall human health: they enhance antioxidant defenses, modulate inflammatory responses, and may even alleviate diseases.

Figure 1. Illustration of gut microbial biotransformation of dietary polyphenols to their metabolites.

A fun fact about PMMs: they can act like a natural “skincare” from within your body!

Here are some common PMMs you can intake from your foods and their potential skin-beneficial effects:

  1. Urolithins: They are PMMs derived from ellagitannins and ellagic acid found in various fruits (e.g. pomegranate) and nuts. They have been studied for anti-cancer and neuroprotective effects. For instance, urolithin A (UA) is reported to be safe and can improve mitochondrial and cellular health in humans [1]. In addition, UA can exert anti-aging effects on human skin fibroblasts [2] and protect skin cells from UVA-induced cellular damage [3].
  2. Equol: This compound is produced from the isoflavonoid daidzein found in soy and other legumes. It exerts estrogenic activity and has been studied for its potential benefits in alleviating menopausal symptoms and reducing bone loss. A microarray/protein-based study showed that equol and its isomers protect human skin cells by modulating the expression of aging and inflammatory genes [4].
  3. Enterolactone and enterodiol: These are PMMs produced from the microbial fermentation of lignans, a group of unique phytochemicals found in flaxseeds, sesame seeds, maple syrup extract, and other plant sources. These metabolites have been linked to potential benefits in reducing the risk of hormone-related cancers [5].
  4. Hydroxyphenylvalerolactones: These PMMs are formed from the breakdown of tea flavonoids (known as catechins) and are thought to contribute to the health benefits of tea. Human clinical studies showed that green tea catechin metabolites including hydroxyphenylvalerolactones can be detected in the skin tissue with skin protective effects against UV-induced inflammation [6].
  5. Simple phenols: These compounds include tyrosol and hydroxytyrosol, which are PMMs of olive and jasmine phenolics, such as oleuropein. A reported study showed that hydroxytyrosol and its parent compound oleuropein are skin permeable and they can inhibit elastase and collagenase (enzymes that cause skin wrinkles) as well as protect skin cells in a synergistic manner [7].

PMMs hold significant promise for skin health. Partially, this is due to their promising biological effects such as antioxidant properties. PMMs can protect the skin from premature aging by neutralizing harmful free radicals. Additionally, their anti-inflammatory capabilities may soothe irritated skin, reducing redness and swelling associated with conditions like acne, eczema, and psoriasis. Some of these metabolites also exhibit antimicrobial properties that can prevent skin infections by inhibiting the growth of pathogens. Beyond these benefits, phenolic metabolites enhance the skin’s barrier function, improving its natural defenses and moisture retention. Incorporating phenolic-rich foods into one’s diet can support the production of these beneficial metabolites, potentially enhancing skin health from within. For example, a recent randomized double-blind placebo-controlled clinical study showed that a pomegranate supplement (i.e. Pomella®) can promote skin health and beauty from within properties by improving biomarkers that are associated with visible wrinkles and moisture in a healthy population. Interestingly, polyphenols in pomegranate and their PMMs are thought to exert synergistic influence on both gut and skin microbiomes [8].

Although the potential of PMMs in skincare is promising, several challenges hinder their application and effectiveness. First, the variability in individual gut microbiota composition means that not everyone produces these beneficial metabolites at the same levels. Additionally, the complexity of accurately studying these metabolites in skin tissue remains challenging. These factors add layers to the barrier of developing PMMs-based topical skincare products. Research and development efforts are directed to effectively deliver these compounds to the skin and to ensure the stability and absorption of PMMs. Lastly, regulatory hurdles related to proving the health claims of such products can slow down their introduction to the market.

The future of utilizing PMMs in skincare is an exciting frontier with immense potential. Efforts are needed to advance our understanding of how these compounds interact with the skin’s microbiome and cellular structures, aiming to enhance their bioavailability and stability for effective topical applications. Collaborative research from all angles including microbiology, dermatology, and cosmetic science is crucial to developing new skincare formulations that harness these promising PMMs. Additionally, the industry is expected to innovate with sustainable and scientifically-backed products that leverage the health-promoting potential of PMMs.

 

References

  1. Andreux, Pénélope A., et al. “The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.” Nature Metabolism 1.6 (2019): 595-603.
  2. Liu, Chun-feng, et al. “Antiaging effects of urolithin A on replicative senescent human skin fibroblasts.” Rejuvenation Research 22.3 (2019): 191-200.
  3. Liu, Wenjie, et al. “Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy.” Journal of Photochemistry and Photobiology B: Biology 232 (2022): 112462.
  4. Lephart, Edwin D. “Protective effects of equol and their polyphenolic isomers against dermal aging: microarray/protein evidence with clinical implications and unique delivery into human skin.” Pharmaceutical Biology 51.11 (2013): 1393-1400.
  5. Adlercreutz, Herman. “Lignans and human health.” Critical reviews in clinical laboratory sciences 44.5-6 (2007): 483-525.
  6. Rhodes, Lesley E., et al. “Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid.” British Journal of Nutrition 110.5 (2013): 891-900.
  7. Li, Huifang, et al. “Dietary polyphenol oleuropein and its metabolite hydroxytyrosol are moderate skin permeable elastase and collagenase inhibitors with synergistic cellular antioxidant effects in human skin fibroblasts.” International Journal of Food Sciences and Nutrition 73.4 (2022): 460-470.
  8. Chakkalakal, Mincy, et al. “Prospective randomized double-blind placebo-controlled study of oral pomegranate extract on skin wrinkles, biophysical features, and the gut-skin axis.” Journal of Clinical Medicine 11.22 (2022): 6724.