Mental Health Care: Exploring the Microbiota-Gut-Brain Connection

By: Kim Ross, DCN, CNS, LDN, IFMCP

1. Introduction
2. What is the Microbiota-Gut-Brain Axis?
3. The Microbiota's Influence on the Gut-Brain Axis
4. The Microbiota-Gut-Brain Axis and Mood
5. Nutrition and Lifestyle Interventions to Support the Microbiota-Gut-Brain Axis
6. Nutrient Solutions to Support the Microbiota-Gut-Brain Axis
7. Pure Encapsulations Nutrient Solutions
8. Conclusion
9. Resources

Introduction

Mental health concerns are a growing global issue, with recent data indicating that nearly 1 in 8 individuals worldwide experience some form of emotional distress, including anxious feelings and mood fluctuations.¹ Evidence suggests that disruptions in gut microbiota composition, often influenced by modern diets, stress and environmental exposures, may play a role in these rising mental health concerns.²

By leveraging dietary strategies, stress management techniques and targeted nutrient support, clinicians can provide natural, sustainable solutions that optimize the microbiota-gut-brain axis to address mental health and emotional resilience.

This blog explores the underlying mechanisms of the microbiota-gut-brain axis, its role in mood regulation and evidence-based strategies, including dietary interventions, stress management techniques and targeted nutrients such as probiotics, prebiotics, ashwagandha and L-theanine to support a balanced and resilient gut-brain connection.^‡

What is the Microbiota-Gut-Brain Axis?

The microbiota-gut-brain axis is a bidirectional communication network between the gut microbiome, the central nervous system (CNS), autonomic nervous system (ANS), enteric nervous system (ENS) and the hypothalamus-pituitary-adrenal (HPA) axis.^3,4 This intricate system regulates cognitive function, mood and overall mental well-being. The gut microbiome, composed of trillions of microorganisms, influences neurotransmitter production, immune modulation and hormonal balance, all affecting neurological function and mental & emotional health.⁴

The Microbiota's Influence on the Gut-Brain Axis

The microbiota-gut-brain axis functions through several key pathways facilitating communication between the gut microbiota and the brain. These include neural, immune and endocrine pathways, each playing a distinct role in supporting mental health.

Neural Pathway

The vagus nerve is a primary conduit between the gut and brain, transmitting signals directly from the gut microbiota to the central nervous system.³ Sometimes called the “sixth sense,” the vagus nerve can sense the microbiota and transfer the information to the nervous system, where it integrates and responds appropriately.⁵ Additionally, the enteric nervous system, often called the "second brain," contains millions of neurons that interact with gut microbes to regulate neurotransmitter production and brain activity.

Immune Pathway

The gut microbiome plays a critical role in immune system regulation, influencing cytokine regulation.³ Beneficial microbes promote the release of anti-inflammatory cytokines, such as interleukin-10 (IL-10). Non-beneficial microorganisms can trigger the production of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which have been implicated in neuro-immune responses and mood disturbances.⁶

Endocrine Pathway

The endocrine pathway is more commonly referred to as the neuroendocrine system. The gut microbiota modulates gut hormones and neurotransmitters made in the gut and activates the hypothalamus-pituitary-adrenal (HPA) axis. The HPA axis governs the body's stress response and is involved in mood and immune function.³ Gut bacteria produce neurotransmitters such as serotonin, dopamine and GABA, which are essential for maintaining emotional stability.⁷

The Microbiota-Gut-Brain Axis and Mood

Studies suggest that gut microbiota imbalances are linked to mood fluctuations through altered neurotransmitter production, increased intestinal permeability, HPA dysregulation and heightened cytokine production. Specific bacterial strains, such as Bifidobacterium longum and Lactobacillus helveticus, have been shown to exert anxiolytic and mood-stabilizing effects by modulating gamma-aminobutyric acid (GABA), serotonin, dopamine, tryptophan, cortisol and cytokines.⁷

Nutrition and Lifestyle Interventions to Support the Microbiota-Gut-Brain Axis

Optimizing gut health through targeted nutrition and lifestyle interventions can strengthen the microbiota-gut-brain axis and improve mood regulation.

Diet and Its Influence on the Microbiome

Diet is described as one of the most influential and rapid contributors to microbial changes.^3,4 A symbiotic relationship between fiber, polyphenols, prebiotics and fermented foods in the diet supports microbial diversity and enhances gut-brain communication.

• Fiber is a food source for beneficial bacteria and promotes short-chain fatty acid (SCFA) production. Among its benefits, SCFAs support the GI barrier, promote the production of serotonin and GABA, modulate the immune system and influence the gut-brain connection through the vagus nerve.⁸ Fruits, vegetables, legumes and whole grains are rich sources of dietary fiber.
• Polyphenol-rich foods like berries, apples, green tea, olive oil and dark chocolate may act as prebiotics.³ They have been shown to modulate the gut microbiome by increasing beneficial bacteria (i.e., Bifidobacterium, Firmicutes, Lactobacillus) and reducing harmful bacteria (i.e., Clostridium) while also supporting the body’s natural inflammatory processes and providing antioxidant and neuroprotective properties.⁹ Many polyphenol-rich foods are also a good source of fiber.
• Prebiotics found in foods like garlic, onions, leeks, bananas, apples, honey, chicory root, flaxseed and asparagus fuel the growth of beneficial bacteria. By default, many prebiotic foods are also a source of fiber and polyphenols.
• Fermented foods, including yogurt, kefir, kimchi, miso, cheese, vinegar and sauerkraut, provide beneficial probiotics that enhance gut microbiota composition and are a readily available source of SCFAs. Homemade fermented foods will provide the most probiotic diversity, and the fermentation process increases the polyphenol bioavailability.¹⁰

In contrast, a diet high in processed foods, refined sugars and artificial additives can disrupt the gut microbiome, contributing to mood fluctuations and an altered cytokine response.⁴

Stress, Physical Activity and Sleep: Their Influence on the Microbiome

Stress negatively impacts gut microbiota composition and vagal tone, increasing intestinal permeability and cytokine response.⁵ Conversely, gut microbiota diversity may influence how one handles stress, partially due to the influence on the production of GABA and serotonin.¹¹ Stress management techniques like meditation, deep breathing and cognitive behavior therapy can help restore microbial balance, reduce HPA overactivity and support emotional resilience.⁵

Physical activity, particularly aerobic exercise, fosters microbial diversity and enhances the production of beneficial short-chain fatty acids (SCFAs), improving HPA axis control and positive moods.¹²

Sleep and the microbiome have a complementary relationship. Sleep is essential for maintaining a healthy microbiome, and a diverse microbiome has been positively correlated with increased sleep efficiency and total sleep time. Sleep deprivation has been linked to shifts in microbial composition and increased cortisol levels.¹³

Nutrient Solutions to Support the Microbiota-Gut-Brain Axis

Targeted supplementation with specific nutrients and bioactive compounds can further enhance the gut-brain connection and promote positive mental health.^‡

Probiotics & Prebiotics

Probiotic supplementation has been extensively studied for its effects on gut health and mood regulation. More specifically, in 2013, the term 'psychobiotics' was coined, describing the beneficial bacteria that produce health benefits for mental health.⁷ Multiple probiotic strains have been shown to enhance GABA and serotonin receptor expression in the brain, reduce cortisol levels and reduce cytokine activation. (Table 1)^‡

The most extensive and compelling evidence to support emotional and mental health exists for Lactobacillus helveticus Rosell-52 (RO052) and Bifidobacterium longum Rosell-175 (RO175).⁷ In a randomized, double-blind, placebo-controlled trial, supplementation with this combination maintained healthy urinary cortisol levels, indicating the potential to lessen occasional stress.¹⁴ In a separate analysis, supplemented subjects reported positive mood, relaxation and enhanced cognitive function.¹⁵ Further, multiple human studies have reported positive mood effects with this specific combination of probiotic strains.⁷

Prebiotics works synergistically with probiotics. The various types of prebiotics include fructans, galactooligosaccharides, xylo-oligosaccharides, chitooligosaccharides, lactulose, resistant starch and polyphenols. Prebiotics modulate and support the growth of the gut microbiota, specifically Bifidobacteria and Lactobacilli, increase SFCA production, improve gut barrier function, modulate the immune system and positively influence mood.^16‡

Butyrate

Butyrate is one of the three most abundant short chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of polysaccharides/fiber in the colon, where it serves as an energy source for epithelial cells.¹⁷ Considered a functionally versatile molecule, butyrate provides support for maintaining gastrointestinal health and regulating the neuro-endocrine-immune pathways, in part due to its ability to cross the blood-brain barrier.^17,18‡

Ashwagandha

Ashwagandha (Withania somnifera) is an adaptogenic herb that modulates the HPA axis and maintains healthy cortisol levels. In a double-blind trial, 60 participants with high perceived stress scores were randomized to receive KSM-66 Ashwagandha^® extract (125 mg or 300 mg) or placebo twice daily for 8 weeks. A significant reduction in perceived stress scale (PSS) scores was observed with both doses of ashwagandha compared to the placebo group. Mean cortisol response decreased by 17% and 33% in the groups receiving 125 mg and 300 mg twice daily, respectively, after 8 weeks. Subjects receiving ashwagandha also exhibited significant improvements in sleep quality.^19‡

L-Theanine

L-theanine an amino acid found in green tea, may be most recognized for its ability to exert anxiolytic effects by modulating GABA activity and for its role in regulating the stress response. In a double-blind crossover trial, 30 healthy adults received l-theanine (200 mg Suntheanine^®/day) or placebo for 4 weeks. L-theanine significantly improved stress-related symptoms, including low-mood symptoms and occasional anxiety per validated questionnaires and sleep (Pittsburgh Sleep Quality Index; PSQI)^‡

Newer research also suggests that l-theanine influences the gut-brain connection by increasing beneficial bacteria, such as Lactobacillus, while also decreasing non-beneficial bacteria, such as Closterium.²¹

Pure Encapsulations^® Nutrient Solutions

Pure Encapsulations provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care and support microbiota-gut-brain axis in your patients.^‡

ProbioMood is a clinically researched combination of probiotic strains that promotes emotional well-being and relaxation. This formula contains the well-researched strains Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175. It was developed using an innovative, patented microencapsulation process designed to protect the probiotic strains from harsh conditions, including gastric acidity.^‡

Suggested Use: Take one (1) capsule daily, with or between meals

Poly-Prebiotic is a shelf-stable prebiotic formula that includes 1.5 g of clinically researched PreticX^™ XOS (xylo-oligosaccharides) that enhances the growth of Bifidobacteria. In contrast to FOS and other common prebiotics, studies on XOS report very low incidence of gas and bloating.^20,21

Suggested Use: Take three (3) capsules, 1-2 times daily, with or between meals

SunButyrate^™-TG liquid is a unique butyrate-rich triglyceride oil that allows for direct delivery of 875 mg of butyric acid (per serving) to the intestines. Benefits include supporting gut cell and barrier function and promoting cytokine balance.^‡

Suggested Use: As a dietary supplement, take 1 teaspoon, 1-3 times daily, with meals.

Daily Calm combines GABA with clinically backed saffron (affron^®), ashwagandha (KSM-66^®) and l-theanine (Suntheanine^®) to relieve feelings of occasional stress and anxiety. Together, these ingredients address common mental health needs while supporting mood and sleep quality with continued use.^‡

Suggested Use: Take one (1) capsule, two times daily between meals

Conclusion

The microbiota-gut-brain axis plays a pivotal role in supporting mental health. The gut microbiota communicates with the brain through neural, immune and endocrine pathways, influencing neurotransmitter production, stress response and cytokine regulation. Healthcare professionals can support gut health and enhance mental well-being by utilizing targeted nutrients such as probiotics, prebiotics, ashwagandha and l-theanine, in combination with diet and lifestyle strategies.

Resources

Microbiota-Gut-Brain Axis Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient's intestinal health.

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

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