The gut-brain axis: what the research shows about gut and mood

The gut-brain axis: what does the research say about gut flora, mood and mental health?

Author: Dr. Bahir Hadi, specialist in surgery, PhD · Date: June 2026

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Summary

The gut-brain axis describes the bidirectional biochemical communication between the central nervous system (the brain) and the enteric nervous system (the gut). Research - primarily from animal studies and smaller human trials - suggests that the composition of gut bacteria can influence brain function, stress response and emotional regulation. The field is developing rapidly, but much of the underlying mechanisms remain research areas rather than established clinical relationships. This article reviews what we know, what remains uncertain, and what the clinical data say about so-called "psychobiotics" for anxiety and depression.

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Introduction

Have you ever had "butterflies in your stomach" when nervous, or felt unwell in your gut under stress? That is not just figurative language - there is a genuine biological communication pathway between gut and brain.

The gut is popularly referred to as a "second brain" because the enteric nervous system contains many nerve cells and can function partly independently. This is, however, a figurative term, not a literal anatomical or functional equivalent to the brain. It has long been known that the brain sends signals down to the gut. More recent research is examining the extent and mechanisms by which signals also travel the other way - from gut bacteria to the brain - but this remains an active research field with many unanswered questions about cause and effect in humans. See also probiotics in capsule form and natural probiotics through food.

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How might the gut communicate with the brain? (research areas)

Preclinical studies (primarily in animal models) and a small number of human trials have proposed several possible pathways by which gut bacteria may influence the central nervous system. It is important to stress that much of this has been shown in animal models and has not yet been fully translated or confirmed in humans.

1. The vagus nerve

The vagus nerve connects the brainstem to the gastrointestinal tract. Animal studies have shown that changes in gut bacteria can affect vagal nerve activity, and that this nerve connects, among other things, to brain areas involved in fear and emotional regulation, such as the amygdala and hippocampus [1]. How significant this is for human behaviour and psychological symptoms remains under investigation.

2. Neurotransmitters and gut-derived serotonin

Gut bacteria can influence the production of signalling molecules. The best documented example is serotonin: in germ-free mice and in cell studies, certain spore-forming gut bacteria increased serotonin production in the enterochromaffin cells of the gut and affected gut motility and platelet function [2]. Those are animal and laboratory data, not treatment trials in humans. Most of the body's peripheral serotonin is produced in the gut, where it mainly has local functions. Peripheral serotonin does not cross the blood-brain barrier and cannot be equated with neurotransmission in the brain. Some gut bacteria can also produce GABA in the laboratory, and the genes for GABA production have been shown to be active in human stool samples. What exists in humans so far is an observed association, not a demonstrated effect on the brain [8].

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

When gut bacteria break down dietary fibre, short-chain fatty acids such as butyrate, acetate and propionate are produced, among other substances. In animal and cell studies, these substances appear to influence inflammation and barrier functions, including parts of the blood-brain barrier [3]. Associations have been observed between low-grade inflammation and depression in clinical populations, but this is an association, and it has not been proven that short-chain fatty acids in the human gut directly prevent or treat depression [4].

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What does the research say about "psychobiotics"?

The term psychobiotics has been proposed in the scientific literature to describe probiotic or prebiotic substances that could theoretically influence mental health via the gut-brain axis [5]. This is a research term for a developing field - not a documented or approved treatment for anxiety or depression.

What do the studies show so far?

A small number of smaller randomised trials with specific probiotic strains have examined effects on anxiety, depression and stress-related symptoms, including in patients with concurrent IBS [6]. Results are mixed and vary with strain, dose, patient group and outcome measure. There is currently no strain or product that can be recommended as a documented treatment for anxiety or depression, and psychobiotics do not replace established psychiatric assessment and treatment.

Diet and microbiome diversity

A controlled study has examined the effect of a diet rich in fermented foods and found an increase in microbiome diversity and a reduction in certain inflammatory markers in healthy participants over a defined period [7]. Findings of this kind are interesting, but a single study in a specific, healthy population is not proof of a general relationship between fermented food and better mental health, and the result is not automatically transferable to patients with anxiety or depression.

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Conclusion

The gut-brain axis is a genuine and active research field, in which biologically plausible communication pathways between gut bacteria and the nervous system have been found - primarily in animal models and smaller human studies. It has not yet been established that anxiety or depression can be treated in a targeted way by altering the gut flora, and "psychobiotics" is not an established clinical treatment. A varied diet, including fermented foods according to individual tolerance if desired, can be part of a healthy lifestyle, but should not be presented as a documented treatment for psychological symptoms. In cases of persistent anxiety or depression, relevant assessment and treatment should be sought from a doctor or psychiatrist/psychologist.

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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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References

1. Cryan JF, et al. The Microbiota-Gut-Brain Axis. Physiol Rev 2019;99(4):1877-2013.
2. Yano JM, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015;161(2):264-76.
3. Dalile B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol 2019;16(8):461-78.
4. Foster JA, Neufeld KM. Gut-brain axis: how the microbiota could influence anxiety and depression. Trends Neurosci 2013;36(5):305-12.
5. Dinan TG, et al. Psychobiotics: a novel class of psychotropic. Biol Psychiatry 2013;74(10):720-6.
6. Pinto-Sanchez MI, et al. Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology 2017;153(2):448-59.
7. Wastyk HC, et al. Gut-microbiota-targeted diets modulate human immune status. Cell 2021;184(16):4137-53.
8. Strandwitz P, Kim KH, Terekhova D, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol 2019;4(3):396-403.