Gut-Brain Axis: How Polyphenols and Prebiotics Support Microbial and Brain Health

The gut-brain axis is a compelling framework linking diet, gut microbiota, immune signaling, and neural function (Cryan et al., 2019). Among dietary strategies, prebiotics (non-digestible fibers and polysaccharides) and polyphenols (plant bioactives) are two promising levers to influence gut ecology and produce neuroactive metabolites. In this article, we'll integrate evidence on matcha green tea (a polyphenol-rich tea) and Agaricus blazei (a medicinal mushroom with potential prebiotic properties), exploring their roles in gut-brain modulation, mechanisms, limitations, and practical suggestions.

Understanding the Gut-Brain Axis

The gut-brain axis involves bidirectional communication between the gastrointestinal (GI) tract and the central nervous system through neural (via the vagus nerve), endocrine, immune, and metabolic pathways (Cryan et al., 2019). It includes the Hypothalamic-Pituitary-Adrenal (HPA) axis, which regulates the body's stress response and is sensitive to signals originating from the gut, particularly inflammatory and microbial metabolites (Cryan et al., 2019).

Disruption in gut barrier function, microbial dysbiosis, or chronic low-grade inflammation can send pro-inflammatory or metabolic signals to the brain, potentially influencing mood, cognition, and neural resilience (Cryan et al., 2019).

Thus, modulating the microbiome in a favorable direction is a plausible partial lever for influencing brain-related outcomes—though causality and optimal strategies remain active research areas.

Prebiotics and the Gut Microbiome: Spotlight on Agaricus blazei

A. What Are Prebiotics & Why Mushroom-Derived Ones Matter

Prebiotics are substrates selectively utilized by host microbiota to confer health benefits—typically non-digestible fibers or oligosaccharides (Slavin, 2013).

Mushroom polysaccharides (e.g., β-glucans) and dietary fiber from mushrooms have increasingly been studied for prebiotic potential: they may increase short-chain fatty acid (SCFA) production and shift microbial communities toward beneficial taxa (Araújo-Rodrigues et al., 2024).

In one review, the consumption of mushrooms and their derived polysaccharides was noted to have potential effects on gut microbiota, immunomodulation, and health outcomes (Araújo-Rodrigues et al., 2024).

B. Evidence for Agaricus blazei / Agaricus blazei Murill

Research explicitly focusing on Agaricus blazei points to interesting effects:

  • In an animal/dietary study, Agaricus blazei extract supplementation (in obese models) modulated gut microbial ecology and improved metabolic parameters (Vincent et al., 2013).
  • One mouse study (via a polysaccharide fraction of Agaricus blazei) found alleviation of DSS-induced colitis, correlated with improved intestinal barrier integrity and metabolic remodeling (Ji et al., 2023).
  • A poultry (broiler) feeding trial using Agaricus blazei stipe (ABS) reported that ABS supplementation improved villus/crypt metrics (intestinal morphology), increased microbial diversity in the cecum, and increased beneficial bacterial proliferation (Ju et al., 2023).

These findings suggest that Agaricus blazei contains polysaccharide fractions (e.g., β-glucans and other fibers) that may function similarly to prebiotics by promoting beneficial microbial shifts, enhancing barrier function, reducing inflammation, and supporting gut health.

For example, third-party analysis of Superfood Science Agaricus Bio 600 mg (lot# VHM25088) found a β-glucan content of 67%, indicating a rich source of prebiotic fibers.

Future Research Directions: Given the limited human data, the critical next step involves isolating and characterizing the specific polysaccharide fractions in A. blazei (like -glucans) and testing their SCFA-producing potential in human fecal in vitro cultures before proceeding to well-powered human intervention trials (Araújo-Rodrigues et al., 2024).

Polyphenols as Gut-Modulating Agents: Spotlight on Matcha Green Tea

A. Matcha: A Concentrated Source of Polyphenols

Matcha is powdered, shade-grown green tea (Camellia sinensis) in which the whole leaf is consumed, resulting in higher bioactive concentration compared to typical green teas (Sivanesan et al., 2021).

It contains catechins (especially epigallocatechin gallate, EGCG), L-theanine, caffeine, and other antioxidants.

Animal and mechanistic studies suggest that matcha may confer neuroprotective, metabolic, and anti-inflammatory effects (Sokary et al., 2022).

B. Gut Modulation by Green Tea Polyphenols / EGCG

While much of the gut-focused evidence is from green tea catechins (especially EGCG), the findings are relevant to matcha, given its high EGCG content:

  • In a murine colitis model, oral EGCG attenuated inflammation and improved barrier integrity in a microbiota-dependent manner, enriching SCFA-producing bacteria such as Akkermansia (Wu et al., 2021).
  • Research suggests that tea polyphenols can modulate the gut microbiome, which may, in turn, contribute to maintaining healthy brain function (Xu et al., 2023).
  • Luo et al. (2024) reported a connection between the gut and metabolism: in mice consuming a high-fat diet, matcha altered the gut microbiota. This shift corresponded with a reduction in obesity and an improvement in metabolic health.

Thus, matcha's polyphenols may act partly by altering the gut microenvironment—increasing beneficial taxa, promoting SCFA production, and reducing gut-derived inflammation.

C. Biotransformation & Neuroactive Metabolites

Most dietary polyphenols reach the colon relatively intact, and gut microbes biotransform them into more minor phenolic metabolites (e.g., urolithins, phenolic acids) that are more bioavailable and may cross the blood-brain barrier (Domínguez-López et al., 2025).

These metabolites modulate oxidative stress, inflammatory pathways (e.g., NF-B, Nrf2), and neuroplasticity.

In short, matcha's catechins may serve as "pro-polyphenols" whose real neuroactive potential is unlocked via microbial metabolism, aligning with the broader model of polyphenol gut-derived metabolites' brain effects (Domínguez-López et al., 2025).

Gut-Derived Metabolites & Brain Signaling

A. SCFAs & Vagus Activation

SCFAs (acetate, propionate, butyrate) generated via microbial fermentation of prebiotics (and perhaps mushroom polysaccharides) support gut barrier integrity, modulate immune signaling, and may engage vagal afferents to influence brain regions (Sharma et al., 2024).

B. Phenolic Metabolites, Inflammation & Neurotransmission

Microbial conversion of polyphenols (e.g., from matcha) yields metabolites that modulate inflammation and oxidative stress, and can influence neurotransmitter pathways (e.g., via NMDA, GABA, BDNF) (Domínguez-López et al., 2025).

Because they may cross the blood-brain barrier, these metabolites could exert direct neurocognitive effects.

C. Barrier Integrity & Immune Crosstalk

A healthier microbiome helps maintain tight junctions and reduce intestinal permeability ("leaky gut"). It limits the translocation of lipopolysaccharide (LPS) and pro-inflammatory molecules into the bloodstream, thereby reducing both systemic and neuroinflammatory loads (Zhang et al., 2024).

Human Evidence & Limitations

While the mechanistic and animal literature is robust, human trials linking prebiotics, polyphenols (such as matcha), gut changes, and cognitive or mood outcomes are scarce.

Some observational evidence suggests that higher polyphenol intake (e.g., from tea and berries) is associated with lower rates of cognitive decline and depression (Serra et al., 2023). For example, a systematic review found a beneficial inverse association between overall polyphenol intake and depressive symptoms (Serra et al., 2023).

To date, there are no well-powered Randomized Controlled Trials (RCTs) specifically examining the prebiotic effects of Agaricus blazei in humans with brain outcomes.

Thus, while matcha and Agaricus blazei are promising candidates, they should be considered adjuncts (not treatments) within a holistic diet.

Practical Considerations for Daily Use

A. Food & Supplement Strategies

Matcha: Use high-quality matcha (ceremonial or premium grade) to benefit from concentrated EGCG + L-theanine. Start with one teaspoon (2 grams) per day, and evaluate tolerance (caffeine effects).

Agaricus blazei: Use certified organic Agaricus blazei mushroom containing polysaccharide-rich fractions. Begin with modest dosages (e.g., of dried mushroom powder or equivalent extract) if tolerable and no contraindications.

Pair these with a diet rich in dietary fiber, colorful vegetables, and other mushroom species to support a diverse microbial ecosystem.

B. Individual Variability

  • Microbial metabotypes vary: Not everyone will convert polyphenols to beneficial metabolites.
  • Gastrointestinal tolerance (gas, bloating) may arise, especially during ramp-up phases.
  • Interactions: high-dose polyphenols or mushroom extracts may interact with medications (e.g., immunomodulators, anticoagulants). Monitor closely.

C. Monitoring & Timeline

  • Give 8–12 weeks or more for microbiome adaptation and functional changes.
  • Monitor subjective outcomes (mood, cognition, GI comfort) and, if available, biomarkers (e.g., inflammatory markers, SCFA profiles).
  • Adjust dosages or rotate sources to sustain microbial stimulation over time.

Conclusion

Incorporating matcha green tea and Agaricus blazei into a gut-centric dietary approach offers an intriguing synergy: matcha as a rich source of polyphenols that contributes to metabolite-mediated brain effects, and Agaricus blazei as a possible mushroom-derived prebiotic that supports beneficial microbes and maintains barrier function.

However, human data—especially linking these interventions directly to brain outcomes—remain limited. Therefore, they should complement broader dietary and lifestyle strategies for gut-brain wellness, rather than relying on them as standalone therapies.

Clinical Note

Clinicians should adopt a food-first approach, starting with matcha teas and whole-food mushrooms, before escalating to concentrated supplements. Monitor for drug interactions (especially immunomodulatory or anticoagulant medications) and GI tolerance. Use laboratory tools (e.g., microbiome profiles, inflammatory markers) if available to tailor interventions.

References

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  4. Ji, Z. H., Song, H., et al. (2023). Agaricus blazei polysaccharide alleviates DSS-induced colitis in mice by modulating intestinal barrier and remodeling metabolism. [Unpublished preprint/conference abstract].
  5. Ju, Y., Huang, L. L., Li, L. Y., Zhao, C. G., Huang, X. H., Ye, J. Q., … Liu, Z. L. (2023). Agaricus blazei Murrill stipe promotes growth by improving anti-inflammatory activity and gut function in broilers. Journal of Animal Feed Science, 33(1), 64–75. https://doi.org/10.22358/jafs/168325/2023
  6. Luo, Y., Zhang, Y., Zhang, J., & et al. (2024). Matcha alleviates obesity by modulating gut microbiota and metabolic pathways in mice. Cell Reports Medicine, 5(3). [preprint / early access]
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  9. Sivanesan, I., Mohan, P., Gomathi, K., & et al. (2021). Retrospecting the antioxidant activity of Japanese matcha: A comparative review. Applied Sciences, 11(11), 5087. https://doi.org/10.3390/app11115087
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