The intricate relationship between gut health and overall well-being has gained significant attention in recent years. The gut microbiome, a complex community of microorganisms residing in our intestines, plays a crucial role in digestion, immunity, and even mental health. For health professionals, understanding the factors that influence gut health is paramount. One such influential factor is the intake of polyphenols, a group of naturally occurring compounds found in plants. This article delves into the science of polyphenols, their impact on gut health, and practical recommendations for incorporating them into patient care.

Top Natural Sources of Polyphenols: Boost Your Patients Health with These Foods

Polyphenols are a diverse group of compounds characterised by the presence of multiple phenol units. They are abundantly present in a variety of plant-based foods, and their intake is associated with numerous health benefits. Some of the primary dietary sources of polyphenols include:

Fruits: Berries (such as blueberries, strawberries, and blackberries), apples, grapes, cherries, and citrus fruits are particularly rich in polyphenols like flavonoids and phenolic acids.
Vegetables: Leafy greens, onions, broccoli, and tomatoes are good sources of various polyphenols.
Tea and Coffee: Both green and black teas are excellent sources of catechins and flavonoids, while coffee contains significant amounts of phenolic acids.
Chocolate: Dark chocolate and cocoa products are notable for their high flavonoid content, particularly flavanols.
Whole Grains: Polyphenols in whole grains, such as oats, barley, and brown rice, include phenolic acids and lignans.
Nuts and Seeds: Walnuts, almonds, flaxseeds, and chia seeds provide a variety of polyphenols.
Spices: Common culinary spices such as turmeric, cloves, and cinnamon are potent sources of polyphenols, including curcuminoids and cinnamic acids

Different Types of Polyphenols Explained: Flavonoids, Phenolic Acids, and More

Polyphenols are broadly categorised into flavonoids and nonflavonoids. Flavonoids, which make up about 60% of dietary polyphenols, are further divided into several subclasses, including flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins. Nonflavonoids include phenolic acids, stilbenes, and lignans.

Examples and Sources

Flavonoids:

Flavonols: Onions, kale, leeks, broccoli, blueberries
Flavanols: Apples, green tea, cocoa, apricots, cherries
Flavones: Parsley, celery
Flavanones: Grapefruit, oranges, lemons
Isoflavones: Soybeans
Anthocyanins: Black elderberries, blackberries

Nonflavonoids:

Phenolic acids: Coffee, fruits, whole grains
Stilbenes: Grapes (resveratrol)
Lignans: Flaxseeds, sesame seeds

How Polyphenols Work: Understanding Their Mechanisms of Action in the Body

Polyphenols exert their health benefits through several mechanisms, including anti-inflammatory, antioxidant, and antimicrobial actions.

Anti-inflammatory Properties

Polyphenols target inflammation in multiple ways, making them highly effective in controlling and reducing the body’s inflammatory response.

Blocking Pro-inflammatory Enzymes
Polyphenols, like those found in turmeric and green tea, inhibit enzymes like COX-2 and iNOS, which are responsible for creating inflammatory molecules. By stopping these enzymes, polyphenols reduce pain, swelling, and other symptoms of inflammation, similar to how common anti-inflammatory drugs work—but naturally!
Regulating Key Inflammatory Pathways
A big part of their action comes from polyphenols’ ability to inhibit the NF-κB and MAPK pathways, which control the release of pro-inflammatory signals in the body. When these pathways are overactive, inflammation spirals out of control, but polyphenols keep them in check.
Suppressing Cytokines
Cytokines are like the messengers that tell your body to launch an inflammatory response. Polyphenols, such as quercetin and resveratrol, help reduce the production of cytokines like TNF-α and IL-1β, which are linked to chronic inflammation.

Antioxidant Properties

Polyphenols work through various mechanisms to combat oxidative stress, offering a multi-faceted defense against cellular damage.

Direct Free Radical Scavenging
Polyphenols act like "scavengers," directly neutralizing free radicals before they can harm cells. Free radicals are unstable molecules that damage proteins, lipids, and DNA, leading to inflammation and disease. Polyphenols, such as those in berries and green tea, donate electrons to stabilize free radicals, preventing this damage at the source.
Boosting Endogenous Antioxidant Defenses
Beyond their direct action, polyphenols also stimulate the body’s own antioxidant systems. Compounds like resveratrol and EGCG (from green tea) activate enzymes such as superoxide dismutase (SOD), glutathione peroxidase, and catalase, which are essential for breaking down harmful oxidative molecules.
Inhibiting Oxidative Enzymes
Certain enzymes in the body, like xanthine oxidase, generate free radicals during metabolic processes. Polyphenols, particularly those in red wine and green tea, inhibit these enzymes, reducing the overall production of free radicals.

Antimicrobial Properties

Polyphenols disrupt the survival and growth of various pathogens and pathobionts, including Escherichia coli, Staphylococcus aureus, and Helicobacter pylori, safeguarding the body from infections and supporting a healthy microbiome.

Disrupting Cell Walls
Polyphenols can weaken or break down the cell walls of harmful bacteria and fungi. By damaging the outer layer of these microbes, compounds like epicatechin (found in cocoa) and tannins (from tea and wine) prevent them from reproducing and spreading. This disruption leads to microbial death, preventing infections.
Inhibiting Enzyme Activity
Many pathogens rely on specific enzymes for survival. Polyphenols, such as quercetin and curcumin, inhibit these enzymes, effectively blocking the microbes’ ability to replicate or produce toxins. This enzymatic interference helps reduce the virulence of bacteria and viruses.
Blocking Adhesion to Host Cells
For infections to occur, microbes must first attach to host cells. Polyphenols like proanthocyanidins (found in cranberries) are known to block this adhesion process. By preventing microbes from sticking to the cells in the digestive or urinary tract, polyphenols can stop infections before they start.
Disrupting Microbial Communication (Quorum Sensing)
Certain bacteria communicate with each other through a process called quorum sensing, which helps them coordinate activities like toxin production and biofilm formation. Polyphenols, such as flavonoids, disrupt these signaling pathways, reducing bacterial coordination and making it easier for the immune system to eliminate them.

Microbiome Interaction with Polyphenols

The interaction between polyphenols and the gut microbiome is a complex and fascinating emerging research area. This relationship is bidirectional: polyphenols can influence the composition and function of the gut microbiome, while the gut microbiome plays a crucial role in metabolising polyphenols, thereby affecting their bioavailability and potential health benefits.

Polyphenol Metabolism by Gut Microbiome:

Strain-Specific Metabolism: The breakdown of polyphenols is highly dependent on specific bacterial species and strains. For instance, the conversion of the isoflavone daidzein to equol is performed by bacteria such as Adlercreutzia equolifaciens and Slackia equolifaciens, among others.
Emerging Research: Our understanding of which bacteria can metabolise polyphenols is continually evolving. New species are being discovered and cultured regularly, making this a dynamic field of study.
Metabolite Production: The gut microbiome transforms polyphenols into various metabolites, some of which may have significant health impacts. For example:

Equol, derived from daidzein, may have anti-cancer properties and reduce menopausal symptoms.
Urolithin-A, produced from ellagic acid, may improve mitochondrial function and have anti-inflammatory effects.
DOPAC, a metabolite of quercetin, may have antioxidant properties.

Impact on Clinical Practice:

Personalised polyphenol interventions hold immense potential, but their effectiveness can hinge on the presence of specific bacterial species in a patient’s gut microbiome. If a patient shows little response to a polyphenol-based treatment, it may be due to a lack of the necessary microbes to metabolise these compounds. While microbiome testing offers valuable insights, it's important for practitioners to recognise that the absence of known polyphenol-metabolising bacteria doesn't necessarily indicate an inability to metabolise polyphenols—many microbial species remain undiscovered. The majority of existing research on polyphenol metabolites has been conducted in vitro or using animal models, leaving a gap in human data that needs to be filled to better understand dosages and side effects. As research evolves, the future of personalised polyphenol therapy looks promising, though this level of customization based on individual microbiome profiles is not yet fully attainable with our current knowledge.

Key Gut Health Markers to Measure Before Using Polyphenols

Accurate assessment of gut health is crucial for managing various gastrointestinal disorders. By utilising microbiome testing, such as the MetaXplore GI Plus from Co-Biome by Microba, in your clinical practice practitioners can understand which intervention to use to better support their patient. Gut markers provide valuable insights into the inflammatory status, microbial composition, and overall functionality of the gut. Here, we explore some of the key gastrointestinal and microbial markers used to evaluate gut health and polyphenol prescription.

Gastrointestinal Markers

Calprotectin: Calprotectin is a protein found in neutrophils, a type of white blood cell. When there is inflammation in the gastrointestinal tract, neutrophils migrate to the site of inflammation and release calprotectin, which can be detected in stool samples. Elevated levels of faecal calprotectin are indicative of gastrointestinal inflammation and are commonly used to diagnose and monitor inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis.

Clinical Relevance: Elevated calprotectin levels suggest active inflammation in the intestines, which may warrant further diagnostic procedures like endoscopy or colonoscopy.
Normal Range: Generally, a calprotectin level below 50 µg/g is considered normal, while levels above this threshold may indicate inflammation.

Lactoferrin: Lactoferrin is another protein present in neutrophils that is released during inflammation. Like calprotectin, it is measured in stool samples to assess intestinal inflammation. Elevated faecal lactoferrin levels are associated with IBD and can help differentiate between inflammatory and non-inflammatory gastrointestinal conditions.

Clinical Relevance: High lactoferrin levels can confirm the presence of intestinal inflammation and are useful in distinguishing IBD from irritable bowel syndrome (IBS).
Normal Range: A lactoferrin level below 7.25 µg/g is typically considered normal.

Microbial Markers

3-Indolepropionic Acid (IPA): IPA is a microbial metabolite produced by gut bacteria from the amino acid tryptophan. IPA is known for its neuroprotective and antioxidant properties. It plays a significant role in maintaining gut barrier integrity and systemic health.

Clinical Relevance: Reduced levels of IPA are associated with increased gut permeability ("leaky gut") and systemic inflammation. Assessing IPA can provide insights into gut barrier function and overall microbial health.
Normal Range: An IPA level above 0.50% of the microbiome is typically considered normal.

Trimethylamine (TMA): TMA is a compound produced by gut bacteria during the digestion of certain nutrients, particularly choline and carnitine found in red meat and other animal products. TMA is converted in the liver to trimethylamine N-oxide (TMAO), which has been linked to cardiovascular health.

Clinical Relevance: Elevated levels of TMA and TMAO are associated with an increased risk of cardiovascular diseases. Monitoring TMA can help assess the impact of diet and gut microbiota on cardiovascular health.

Normal Range: A TMA level below 3% of the microbiome is typically considered normal.

Learn more about these gastrointestinal and microbial markers by listening to this podcast.

Using Polyphenols to Address Gut Health Markers

Polyphenols, with their diverse health-promoting properties, offer a promising avenue for addressing various gut health markers. By modulating inflammatory responses, enhancing antioxidant defences, and altering microbial composition, polyphenols can positively impact markers such as calprotectin, lactoferrin, IPA, and TMA.

Targeting Calprotectin and Lactoferrin with Anti-inflammatory Polyphenols

Inflammatory markers like calprotectin and lactoferrin are crucial for diagnosing and monitoring gastrointestinal inflammation. Polyphenols with potent anti-inflammatory properties can help reduce these markers, thereby alleviating inflammation in the gut.

Curcumin: Curcumin, the active compound in turmeric, is well-documented for its anti-inflammatory effects. It inhibits the NF-kB pathway, which plays a central role in inflammatory responses. By reducing the production of pro-inflammatory cytokines, curcumin can lower levels of calprotectin and lactoferrin.

Clinical Application: Curcumin supplements or turmeric-rich foods can be recommended to patients with elevated calprotectin and lactoferrin levels.

Ellagic Acid: Ellagic acid, found in Kakadu plum powder, pomegranate powder, berries, and nuts, also exhibits strong anti-inflammatory properties. It can inhibit inflammatory pathways and reduce oxidative stress, leading to lower inflammatory markers.

Clinical Application: Incorporating ellagic acid-rich foods into the diet or using supplements can help manage inflammation and reduce calprotectin and lactoferrin levels in patients with gastrointestinal conditions.

Recommendations for Health Professionals

To optimise patient outcomes, health professionals should consider the following guidelines when incorporating polyphenols into dietary recommendations.

Guidelines

Balanced Diet: Emphasise a varied diet rich in different polyphenol sources to support gut and systemic health.
Personalised Approach: Tailor polyphenol recommendations based on individual patient needs, conditions, and diagnostic markers.

Specific Treatment Recommendations

Eat a Variety of Colourful Vegetables Daily: Aim to consume at least 5 different coloured vegetables every day (e.g., red peppers, green spinach, yellow squash, orange carrots, and purple eggplant) to ensure a diverse intake of polyphenols.

Incorporate Berries into Your Breakfast: Add 1/2 cup of mixed berries (blueberries, raspberries, blackberries, strawberries) to your breakfast at least 5 times a week.

Use Pomegranate Powder: Add 1 teaspoon of Pomegranate powder to smoothies and water daily.

Use Herbs and Spices in Cooking: Include 1 teaspoon of polyphenol-rich herbs and spices (such as cloves, rosemary, thyme, ginger, and turmeric) in your meals at least 4 times a week.

Switch to Extra Virgin Olive Oil: Replace your regular cooking oils with extra virgin olive oil for all cooking and salad dressings.

Add Nuts and Seeds to meals: Add a handful (about 30g) of polyphenol-rich nuts (such as hazelnuts, pecans, or almonds) and seeds (such as flaxseeds) to one meal daily.

Use Kakadu Plum Powder: Add 1 teaspoon of Kakadu Plum powder to smoothies and water daily.

Drink Green Tea: Replace one of your daily beverages with a cup of green tea at least 5 times a week.

Add Cacao to Your Diet: Incorporate 1 tablespoon of raw cacao powder into your diet 3 times a week (e.g., in smoothies, hot chocolate, or chia pudding).

Include Flaxseed in Meals: Add 2 tablespoons of ground flaxseed to your daily diet, such as in oats, smoothies, or yogurt.

Follow a Mediterranean Diet: Adopt a Mediterranean-style diet, focusing on polyphenol-rich foods like fruits, vegetables, nuts, seeds, whole grains, and olive oil, for at least 30 days.

Never Mix Banana and Berries

While bananas and berries are both nutritious, they don’t always play well together in a smoothie! The reason lies in the interaction between polyphenols in berries and polyphenol oxidase, an enzyme abundant in ripe bananas. This enzyme degrades the antioxidant-rich polyphenols found in berries, potentially reducing their health benefits. Polyphenols are essential for reducing inflammation and supporting gut health, but when mixed with ripe bananas, you could be losing some of their potency. For a better antioxidant boost, try swapping the banana for frozen zucchini, which adds creaminess without interfering with the polyphenols in your berries!

Microbiome Testing and Polyphenols

Microbiome testing provides invaluable insights into the diversity and composition of your patient’s gut microbiome, allowing you to make more precise decisions when prescribing polyphenols. Understanding which microbial species are abundant or lacking helps you tailor polyphenol supplementation to each patient’s unique microbiome, optimising therapeutic outcomes.

For example, polyphenols like those in Kakadu Plum or Pomegranate Extract require specific bacteria for their metabolism into bioactive compounds that support gut health. Additionally, testing can identify pathogenic imbalances or microbial overgrowth that may impact polyphenol metabolism and overall gut health. In such cases, polyphenol-rich supplements can serve as a tool to modulate the microbiome, reducing harmful bacteria, improving gut barrier function, and addressing inflammation.

By integrating microbiome testing, such as the MetaXplore GI Plus from Co-Biome by Microba, into your clinical practice, you can personalise polyphenol interventions based on robust, data-driven insights. This approach ensures that you maximize the therapeutic potential of polyphenols in improving gut health and addressing your patients’ specific clinical needs.

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Why Polyphenols Are Essential for Gut Health: Key Takeaways

Polyphenols offer a promising avenue for enhancing gut health and overall well-being. By incorporating a variety of polyphenol-rich foods into patient diets, health professionals can leverage the anti-inflammatory, antioxidant, and antimicrobial properties of these compounds to support the gut microbiome and mitigate systemic inflammation. Continued research and personalised approaches will further unlock the potential of polyphenols in clinical practice, ultimately improving patient outcomes and promoting optimal health.

Dr Brad Leech

Brad is a PhD-qualified Clinical Nutritionist and Herbalist specialising in chronic autoimmune conditions and complex gastrointestinal disorders. He provides complete and personalised care to his patients using functional nutrition, integrative medicine and holistic wellness.

The Ultimate Guide to Polyphenols: Science-Backed Benefits for Gut Health