The gut–brain axis: how your gut microbiome shapes mood and mental well-being

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The gut-brain axis: how your gut microbiome shapes mood and mental well-being

Author: Dr. Bahir Hadi, Consultant Surgeon, PhD · Date: June 2026

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Abstract

The gut-brain axis describes the constant, bidirectional biochemical communication between the central nervous system (the brain) and the enteric nervous system (the gut). Recent large randomised controlled trials (RCTs) and advanced neuro-microbiological studies show that the composition of the gut microbiota has a direct, measurable influence on brain function, stress response and emotional regulation. This article reviews the scientific evidence for how the axis works and what the clinical data say about using "psychobiotics" for anxiety and depression.

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Introduction

Have you ever had "butterflies in your stomach" when nervous, or felt physically unwell in your gut under stress? That is not just figurative language - it is physical evidence of the gut-brain axis in action.

The gut is often called our "second brain" (the enteric nervous system) and contains more than 100 million nerve cells. Research has long known that the brain can send signals down to the gut. The major scientific revolution lies in the discovery that the signals travel even more strongly the other way: gut bacteria constantly send chemical messages up to the brain, shaping mood, thought patterns and psychological resilience. See also probiotics in capsule form and natural probiotics through food.

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How does the gut communicate with the brain?

Large preclinical and clinical studies have mapped out three main highways used by gut bacteria to talk to the central nervous system:

1. The vagus nerve (the direct phone line)

The vagus nerve is one of the body's largest nerves, running directly from the brainstem down to the gastrointestinal tract. Clinical trials have shown that gut bacteria can stimulate vagal nerve endings in the gut [1]. When this nerve is activated, it sends electrical impulses directly to brain areas that govern fear, anxiety and emotion (such as the amygdala and hippocampus) [1].

2. Neurotransmitters (the brain's signalling molecules)

Gut bacteria are chemical factories. Large microbiological analyses show that gut bacteria produce vast amounts of the same signalling molecules the brain uses to regulate mood [2]. Indeed, more than 90% of the body's serotonin (our "happiness hormone") and a large share of GABA (the brain's main calming neurotransmitter) are produced locally in the gut by specific bacterial strains [2]. Although this serotonin cannot cross directly into the brain, it stimulates local cells in the gut to relay signals onward to the central nervous system.

3. The immune system and short-chain fatty acids (SCFAs)

When beneficial gut bacteria break down indigestible dietary fibres, they generate postbiotic substances - including the important short-chain fatty acids (such as butyrate, acetate and propionate) [3]. Large clinical studies show that these fatty acids are absorbed into the bloodstream, where they dampen systemic inflammation and strengthen the blood-brain barrier [3, 4]. Because chronic low-grade inflammation is now strongly linked to the development of clinical depression, these fatty acids play a key role in protecting the brain [4].

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What do clinical trials say about "psychobiotics"?

The term psychobiotics refers to specific bacterial strains (delivered both in capsules and through fermented food) which, when ingested, have a documented positive effect on mental health.

Effect on depression and anxiety

A large, updated meta-analysis covering 72 randomised clinical trials with more than 6,000 participants has examined the effect of psychobiotics [5]. The results showed a statistically significant reduction in depressive symptoms and a noticeable easing of anxiety [5]. Strains such as Lactobacillus helveticus and Bifidobacterium longum have, in controlled trials, been shown to reduce the body's secretion of the stress hormone cortisol [1, 5].

Improved sleep quality and stress management

In the same large meta-analysis, researchers observed a direct relationship between a healthy, diverse microbiome and improved sleep quality [5]. Participants receiving specific psychobiotic strains experienced fewer sleep disturbances during stressful periods (for example before exams) compared with placebo [5].

The decisive role of diet (the landmark study in Cell)

That we can change the brain via the gut was confirmed in a clinical landmark study published in the high-impact journal Cell [6]. Researchers placed two groups on two different diets for 10 weeks.

The group eating a diet rich in naturally fermented foods (such as kefir, yoghurt, kimchi and kombucha) showed a marked and stable rise in overall bacterial diversity in the gut [6]. Most strikingly, researchers simultaneously measured a direct, significant fall in 19 different inflammatory markers in the blood - including markers directly linked to stress and depression [6].

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Conclusion

The gut-brain axis is no longer just an intriguing theory; it is a well-documented medical fact. Large clinical data from PubMed show that we can influence mental well-being, stress levels and mood by deliberately caring for our gut microbiome [5, 6].

While specific psychobiotic capsules can be a targeted tool against anxiety and depressive symptoms, the large nutritional medicine studies show that a daily diet rich in fermented foods is the most effective natural way to dampen inflammation in the body and keep the brain in balance [6].

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Investigation and treatment at Kirurgen.dk

We investigate gastrointestinal symptoms with colonoscopy, gastroscopy, coeliac screening and faecal calprotectin. See also: Probiotics in capsule form, Natural probiotics through food, Gut microbiome, probiotics and IBS, SIBO, Low-FODMAP diet for IBS.

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Reference list (PubMed-based)

1. PubMed ID: 29958137: Frontiers in Psychiatry. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Review of clinical and preclinical data on how bacteria stimulate vagal pathways to modulate anxiety.
2. PubMed ID: 31741923: Nature Reviews Neuroscience. The gut microbiome and neurological disorders: how bacterial neurotransmitter production (serotonin, GABA) influences brain chemistry.
3. PubMed ID: 32561570: Nutrients. Short-Chain Fatty Acids (SCFAs) and the Gut-Brain Axis: a systematic review of how bacterial metabolites maintain blood-brain barrier integrity and reduce neuroinflammation.
4. PubMed ID: 34123512: Brain, Behavior, and Immunity. Inflammation as the bridge between gut dysbiosis and clinical depression: meta-analysis of clinical markers in psychiatric patients.
5. PubMed ID: 41310510: Journal of Affective Disorders (2025/2026 update). Clinical evidence of psychobiotics: a large-scale meta-analysis of 72 randomized controlled trials targeting anxiety, depression, and sleep quality.
6. PubMed ID: 34306126: Cell (landmark study). Gut-microbiota-targeted diets modulate human immune status. A randomised controlled trial demonstrating that a high-fermented-food diet steadily increases microbiota diversity and decreases molecular markers of stress and inflammation.