Gut Microbiome and Anxiety: The Gut-Brain Axis in Functional Medicine

When the Gut Speaks to the Mind

How often do we hear or say the phrase «stress upset my stomach» or «I had a knot in my stomach»? While these expressions may sound merely metaphorical, modern science has revealed something far more substantial: the gut truly affects the brain, and vice versa. This dialogue between gut and brain is not just linguistic; it has a clear organic and biochemical foundation.

The gut microbiome, that is, the collection of microorganisms living in our digestive system, has been shown to play a role in various aspects of mental health. Anxiety disorder is one of the most common mental conditions worldwide, affecting millions of people of all ages. For many, symptoms begin without any apparent cause or family history.

However, understanding these symptoms gains depth when we consider the role of the gut and the microbiome. Today, medical research highlights the gut-brain axis as a key pathway linking the gut microbiome to emotional regulation. Studies from the past three years strengthen the hypothesis that alterations in the gut microbiome can trigger, worsen, or destabilize mental balance.

Functional medicine, which views health as the result of interaction among multiple systems, offers a framework that focuses not only on diagnosis but also on causes, mechanisms, and personalized interventions. Within this framework, we approach anxiety disorders not only through symptoms but also by analyzing the microbiome, inflammation, neuroendocrine balance, and nutrition. When the gut is not functioning correctly, mood often follows.

How the Microbiome Influences Anxiety

Communication between the gut and the brain is a multilayered, interactive system involving neural, endocrine, and immune pathways. The primary channel of communication between the gut and brain is the gut–brain axis, through which the microbiome directly influences the regulation of mood and anxiety.

The Vagus Nerve and Serotonin
The vagus nerve transmits signals from the gut to the brain. Metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFAs) and neuroactive molecules like serotonin, influence brain function. It is estimated that about 90% of the body’s serotonin is produced in the gut, under the influence of specific microbial populations. The microbiome, therefore, acts as a regulatory factor in neuroenteric communication, modulating vagal nerve activity and influencing neurotransmitters and brain regions associated with mood, anxiety, and emotional behavior.
Tryptophan, an essential amino acid and the precursor of serotonin, is a critical regulator of mental balance. Under inflammatory conditions, tryptophan is metabolized not into serotonin but into kynurenine, a neurotoxic compound associated with anxiety and depressive mood. The microbial composition of the gut largely determines the direction of this metabolic pathway by influencing the enzymes of the kynurenine pathway, and therefore how much tryptophan is converted into serotonin or inflammatory metabolites. As a result, microbial dysbiosis can promote a biochemical environment that favors neuroinflammation and anxious behavior.

The HPA Axis and the Stress Hormone
Cortisol is the body’s primary stress hormone, produced through the hypothalamic–pituitary–adrenal (HPA) axis. Under normal conditions, cortisol levels are typically high in the morning and low in the evening, following a circadian rhythm that helps maintain stable energy levels and regulate proper sleep.

When stress becomes chronic, cortisol loses its natural rhythm, remaining either consistently elevated or abnormally low. This dysregulation affects mood, sleep, and immune function.
The gut microbiome plays a key role in this process. Microbial imbalance (dysbiosis) can overstimulate the HPA axis and increase cortisol production, while a healthy microbiome helps restore the body’s normal stress response. Measuring salivary cortisol at different times of the day allows assessment of this rhythm and provides valuable information for targeted interventions in functional medicine.

Neurotransmission and Brain Plasticity
The microbiome, through microbial enzymes and metabolites, influences not only serotonin production but also the regulation of other neurotransmitters such as GABA (gamma-aminobutyric acid), which reduces neural overactivity and promotes a sense of calm. At the same time, through the production of B-complex vitamins and short-chain fatty acids, the microbiome enhances neuroplasticity — the brain’s ability to adapt, learn, and recover from stress. A balanced microbiome, therefore, supports both the chemistry of mood and the functional flexibility of the brain.

Chronic Inflammation and Intestinal Permeability
Low-grade inflammation and intestinal barrier leakage (leaky gut) allow toxins to enter the bloodstream. This activates the immune system, increases cytokine levels (IL-6, TNF-α, CRP), and ultimately leads to neuroinflammation, affecting brain areas such as the amygdala and the hippocampus. When the gut microbiome loses its balance, this inflammatory process is further promoted, as beneficial bacteria and the substances that normally strengthen the intestinal barrier are reduced.

Generalized Anxiety Disorder (GAD) and the Microbiome
Of particular interest is the association between the gut microbiome and Generalized Anxiety Disorder (GAD). Recent studies have shown that individuals with GAD exhibit reduced microbial diversity and metabolic alterations in the microbiome, which are linked to increased inflammatory activity and changes in stress regulation. Dysbiosis appears to alter tryptophan metabolism and enhance neuroinflammation by increasing the production of kynurenine, which affects the function of the amygdala and the prefrontal cortex, two brain regions involved in regulating anxiety.

Functional Medicine in the Management of Anxiety Disorders

Functional medicine seeks to understand why a disorder occurs, not only how to suppress its symptoms. Possible underlying causes of an anxiety disorder, along with laboratory methods for investigating them, include:

1. Gut Dysbiosis
Through the EnteroScan® test panel, it is possible to map:

• The microbial balance
• The production of short-chain fatty acids (SCFAs)
• The presence of inflammatory markers

It can also reveal an overrepresentation of specific bacterial groups, such as Proteobacteria, and a deficiency of probiotic species, such as Lactobacillus.

2. Inflammatory Burden
Tests such as hsCRP, IL-6, and TNF-α help detect subclinical inflammation, even when no apparent disease is present.

3. Nutritional Deficiencies
Tests of the NutriScan® and Metals & Traces® panels identifiy deficiencies in:

• Vitamins (suxh as B6, B12, and D)
• Magnesium, zinc, and iron
• Coenzymes related to neurotransmitter production
   

4. Cortisol Regulation
Salivary cortisol measurements at four points throughout the day provide a picture of HPA axis function and stress resilience.

Diet, Lifestyle, and Microbiome Support

Probiotics and Prebiotics

• Probiotic foods: yogurt, kefir, sauerkraut, kombucha
• Prebiotic foods: leek, garlic, oats, banana

Avoid Substances That Burden the Microbiome

• Excess sugar, caffeine, and artificial sweeteners
• Processed foods and trans fats

Circadian Rhythm

• Maintain a consistent sleep schedule
• Get morning exposure to natural light
• Limit screen use in the evening

Exercise

• Walking, light aerobic activity, or yoga
• Research shows a positive impact on both the microbiome and mood

Stress Management

• Breathing techniques, meditation, and psychotherapy
• Support cortisol balance and HPA axis regulation

Learn more here: “Mini Prevention Guides: How to Support Your Microbiome in 7 Simple Steps”

Conclusion

Mental health is not merely a matter of neurochemistry or “personality.” It is the result of our entire biological state, and the gut plays a significant role in this balance. Functional medicine provides a preventive and personalised therapeutic approach.

If you experience symptoms of anxiety, digestive discomfort, unexplained fatigue, or mood disturbances, the solution may not lie solely in the brain — but also in the gut.

What You Can Do Today

• Discover what is really happening in your body with an EnteroScan®, a specialized functional microbiome analysis that reveals essential insights into your gut and immune balance.
• See how Functional Medicine can help in practice — by identifying the root causes of symptoms, rather than simply masking them.
• Subscribe to our newsletter to be the first to receive updates on new preventive tests, wellness articles, and practical guidance from Diagnostiki Athinon.

References

1. Husain, M.I., & Giacobbe, P. (2025). Innovations in the Treatment of Mood Disorders: Exploring Microbiome, Digital and Culturally Adapted Approaches. The Canadian Journal of Psychiatry.
2. Amath, S., Sokolenko, E., Clark, S.R. et al. (2025). Distinguishing the causative, correlative and bidirectional roles of the gut microbiota in mental health. Nature Mental Health.
3. Rabbia, V., De Palma, G., Potts, R., et al. (2025). Altered microbial carbohydrate metabolism is associated with anxiety and gastrointestinal symptoms in patients with Generalized Anxiety Disorder. medRxiv.
4. Castanon, N., Vancassel, S., Amadieu, C., et al. (2025). Obesity-induced emotional alterations in mice are associated with impairments of tryptophan metabolism along the kynurenine and indole pathways. Brain, Behavior, and Immunity.
5. Oyovwi, M.O., Ajayi, A.F. (2025). A comprehensive review on immunological mechanisms and gut-brain pathways linking gut health and neurological disorders. Discover Medicine.
6. Wu, C., Li, X., Wang, H., Liu, Z. (2025). Altered Gut Microbial Diversity and Depletion of SCFA-Producing Taxa Associated with ASD-like Phenotypes in a Prenatal VPA Rat Model. International Journal of Molecular Sciences.

At Diagnostiki Athinon, we treat prevention with the seriousness it deserves. This is where science meets personalized care.