The Gut-Brain Axis: Microbiome Insights into Mental Health by Ori Scott M.Sc. Nutrition Science RD (IL)

The big picture

Over the past five years, researchers have become increasingly interested in the connection between the gut microbiome and mental health, particularly depression and anxiety.

The evidence suggests there really is a connection. However, scientists have not proven that an unhealthy microbiome directly causes depression or anxiety, and microbiome treatments should not replace established mental-health care.

A useful way to think about it is:

Food → gut bacteria → substances produced by bacteria → immune/nervous-system signals → brain

This communication goes in both directions. Stress and mental health can also affect digestion and the gut microbiome.

First, what exactly is the microbiome?

Your digestive tract contains trillions of microorganisms, including bacteria, viruses and fungi.

Collectively, this community is called the gut microbiota.

The gut microbiome technically refers to the microorganisms plus their genetic material, although the terms microbiota and microbiome are often used interchangeably.

These organisms aren't simply passengers. Some help:

• break down components of food

• ferment dietary fiber

• produce useful compounds

• interact with the immune system

• maintain the intestinal barrier

• influence inflammation

• communicate indirectly with the nervous system.

Researchers call the communication system connecting the intestines and brain the microbiota–gut–brain axis.

What does this have to do with depression?

One important 2023 systematic review and meta-analysis examined 44 studies, involving 2,091 people with depressive disorders and 2,792 people without depression. Researchers found differences in the gut bacterial communities of people with depression.

Terminology: systematic review

A systematic review means researchers don't simply select a few studies they like.

They establish rules for searching the scientific literature and systematically identify and evaluate studies that meet those rules.

Terminology: meta-analysis

A meta-analysis goes another step. Researchers statistically combine results from multiple studies to estimate the overall effect.

Generally, a good systematic review/meta-analysis gives us stronger evidence than relying on one small study.

What differences are researchers finding?

There isn't one particular bacterium responsible for depression.

That's important.

Instead, studies suggest that people experiencing depression sometimes have different patterns or communities of bacteria compared with people without depression.

One particularly interesting finding involves bacteria that produce substances called short-chain fatty acids.

What are short-chain fatty acids?

When certain gut bacteria digest—or more accurately, ferment—fiber, they produce compounds called:

SCFAs = short-chain fatty acids

The three major ones are:

• acetate

• propionate

• butyrate 

Butyrate has attracted particular attention.

It provides energy to cells lining the colon and appears to participate in intestinal-barrier regulation, immune activity and inflammation.

Some depression research has reported reductions in bacteria associated with production of these beneficial metabolites.

That gives researchers a possible biological pathway:

Fiber-rich foods → bacteria ferment fiber → SCFAs such as butyrate → effects on gut barrier and immune system → signals that may influence the brain

But we should not turn that into:

"Low butyrate causes depression."

The research isn't strong enough to make that conclusion.

How can your intestines possibly communicate with your brain?

There probably isn't one mechanism. Several systems appear to operate together.

1. The vagus nerve

The vagus nerve is a major communication pathway connecting the brain with organs including the digestive tract.

Think of it as part of the communication highway between the gut and brain.

2. The immune system

Gut microorganisms interact continuously with our immune system.

Changes in the intestinal environment can influence inflammatory signaling.

Chronic inflammation is also being investigated as one biological component of depression in some people.

3. Microbial metabolites

Metabolites are substances produced when organisms carry out chemical processes.

Gut bacteria produce many metabolites from food.

SCFAs such as butyrate are one example.

4. Tryptophan

Tryptophan is an essential amino acid found in protein-containing foods.

Our bodies use it in several pathways, including the production of serotonin.

Gut microorganisms may influence how tryptophan is metabolized.

That does not mean eating more tryptophan or changing one bacterium automatically increases serotonin in the brain. The system is much more complicated.

5. The HPA axis

You'll see HPA axis frequently in this research.

It stands for:

Hypothalamic–Pituitary–Adrenal axis

This is one of the body's major stress-response systems.

Gut microorganisms, inflammation, stress hormones and the nervous system appear to interact with this system.

What are probiotics?

This is probably the area that receives the most public attention.

Probiotics are live microorganisms that, when given in adequate amounts, provide a health benefit.

Common probiotic organisms studied include bacteria from groups such as:

LactobacillusandBifidobacterium

Some researchers use another term:

Psychobiotics

A psychobiotic generally refers to a probiotic or other microbiome-targeted intervention being investigated for possible mental-health benefits.

It is an exciting research concept, but "psychobiotic" does not mean "natural antidepressant."

Do probiotics actually improve depression?

Possibly—and this is one of the more encouraging areas of research.

A 2021 systematic review examined 16 randomized controlled trials involving 1,125 patients. Some depression measures improved with probiotics, although other depression and anxiety measures did not. The authors therefore concluded that probiotics may help but that larger and longer studies were needed.

More recent evidence has strengthened the signal somewhat.

A 2025 systematic review specifically examining people clinically diagnosed with depression or anxiety included 23 randomized trials involving 1,401 patients. Probiotics were associated with reductions in depression and, to a lesser extent, anxiety symptoms. However, results varied substantially among studies.

And a major 2026 umbrella review examined 30 previous systematic reviews/meta-analyses. It found fairly consistent evidence of improvement in major-depression symptoms with probiotics, while results for anxiety were considerably less consistent.

What is an umbrella review?

It's essentially:

a review of systematic reviews.

Instead of combining individual clinical trials, researchers examine the systematic reviews and meta-analyses that already summarized those trials.

It's near the top of the evidence hierarchy.

But there's an important catch here: the 2026 umbrella review found that 76.6% of the reviews were rated moderate, low or critically low in methodological quality. 

So there is a promising signal, but still substantial uncertainty.

What about anxiety?

The picture is less clear.

Some studies show improvement. Others don't.

For example, the 2021 review found improvement using one commonly used anxiety questionnaire but not another.

The 2026 umbrella review similarly found that anxiety results were inconsistent, even though certain groups showed modest improvement.

Therefore, I would summarize the current evidence as:

Depression: 🟢 Promising evidence for probiotics as an additional treatment.

Anxiety: 🟡 Possible benefit, but evidence is less consistent.

Replacement for psychotherapy/medication: 🔴 Not supported.

Probiotics, prebiotics and synbiotics are different

These terms get confused frequently.

Probiotic

The microorganism itself.

Examples include specific strains of Lactobacillus or Bifidobacterium.

Think:

Probiotic = bacteria

Prebiotic

A substance that beneficial microorganisms can use.

Many prebiotics are specific types of fermentable carbohydrate/fiber.

Think:

Prebiotic = food for bacteria

Synbiotic

A combination of probiotics and prebiotics.

Think:

Synbiotic = bacteria + something supporting those bacteria

The recent evidence is stronger for probiotics than prebiotics alone. The 2025 review found significant improvement in depression with probiotics, whereas the result for prebiotics wasn't statistically significant.

The 2026 umbrella review reached a similar conclusion: evidence for probiotics was more convincing, while evidence for prebiotics and synbiotics remained insufficient or inconsistent.

Does that mean everyone with depression should buy probiotics?

No.

There's a major problem with interpreting the probiotic research.

A probiotic isn't one substance.

Different studies use different:

• species

• strains 

• combinations of strains

• doses

• treatment durations

• patient populations.

What is a strain?

Think about dogs.

A Chihuahua and a German Shepherd are both dogs, but they aren't identical.

Bacteria are similar.

Two bacteria can belong to the same species but have different strains, and those strains can behave differently.

A 2024 meta-analysis specifically investigating strain differences found that several Lactobacillus and Bifidobacterium strains appeared in trials reporting improvements, but results also depended on which depression scale was used.

Therefore:

"Probiotics help depression"

is too broad.

A more scientifically accurate statement is:

Certain probiotic strains or combinations may modestly improve depressive symptoms in some populations, but researchers haven't established one universal probiotic prescription for depression.

What about diet?

This may ultimately be more useful clinically than focusing exclusively on supplements.

A 2025 systematic review and meta-analysis in Annals of Internal Medicine evaluated randomized trials lasting at least three months to determine whether dietary interventions affected depression and anxiety.

Diet and microbiome research overlap because what we eat provides substrates for intestinal microorganisms.

In practical terms, a microbiome-supportive dietary pattern generally emphasizes foods such as:

• vegetables

• fruit

• beans and lentils

• whole grains

• nuts and seeds

• other fiber-rich plant foods

• fermented foods when appropriate and tolerated.

The important scientific distinction is that we have evidence connecting dietary interventions with mental-health outcomes, and evidence connecting diet with the microbiome. But we cannot yet say that dietary improvement treats depression specifically because it changed the microbiome.

That's still being investigated.

A few research terms worth knowing

RCT — Randomized Controlled Trial: Participants are randomly assigned to different treatments. This helps researchers determine whether an intervention actually caused an effect.

Placebo: An inactive comparison treatment designed to look like the treatment being studied.

Association: Two things occur together. It does not prove one caused the other.

Causation: Evidence that changing one factor actually produces a change in another.

Heterogeneity: The studies produced quite different results from one another. High heterogeneity lowers our confidence that the same result will occur for everyone.

Dysbiosis: An alteration in the microbial ecosystem sometimes associated with disease. It's commonly described as an "imbalance," although that simplification can be misleading because there isn't one universally defined "perfect" microbiome.

Diversity: The variety of microorganisms within a microbial community. Greater diversity can sometimes be associated with health, but more diversity isn't automatically better in every situation.

CFU — Colony Forming Units: A traditional way of expressing the amount of viable microorganisms in a probiotic.

What I would take away from the research

The scientific evidence from the last five years supports the existence of a gut–brain relationship. People with depression often show differences in their gut microbial communities, and several biologically plausible pathways could connect the microbiome with the brain.

Probiotics are particularly interesting. Recent systematic reviews suggest they may provide additional improvement in depressive symptoms, but studies differ substantially in their strains, doses, participants and methods. Anxiety evidence is less consistent.

Diet also deserves attention. A 2025 systematic review of randomized trials evaluated longer-term dietary interventions for depression and anxiety, supporting continued investigation of nutrition as part of mental-health care.

The appropriate clinical message therefore isn't "heal your gut and cure depression." It's:

Gut health appears to be one piece of a much larger mental-health puzzle. Nutrition and possibly selected probiotics may complement established treatment, but they should not be presented as replacements for psychotherapy, medication, physical activity, sleep management, social support or appropriate medical care.

Foods and eating patterns associated with better mental health

1. Mediterranean-style eating — strongest overall evidence. This pattern emphasizes vegetables, fruits, beans/lentils, whole grains, nuts, seeds, olive oil and fish, with fewer highly processed foods. A 2024 meta-analysis of randomized trials found Mediterranean-diet interventions reduced depressive symptoms, although the certainty of evidence was rated low because the trials were relatively small and differed considerably.

2. Vegetables and fruits. These provide fiber, folate, potassium, polyphenols and other compounds. Rather than recommending one special fruit or vegetable, evidence supports eating a variety as part of a high-quality dietary pattern.

3. Beans, lentils and other legumes. They provide fiber, protein and fermentable carbohydrates. Gut bacteria can ferment some fibers and produce short-chain fatty acids (SCFAs) such as butyrate. These metabolites are being investigated for their roles in the intestinal barrier, immune system and gut-brain communication.

4. Whole grains. Oats, barley, whole-grain bread, brown rice and similar foods provide fiber and other nutrients. Again, their strongest evidence comes from their contribution to an overall high-quality dietary pattern rather than evidence that one particular grain treats depression.

5. Nuts and seeds. Walnuts, almonds, pistachios, chia, flax and other nuts/seeds fit well within dietary patterns associated with better health. They provide unsaturated fats, fiber and micronutrients.

6. Fish, particularly oily fish. Salmon, sardines, trout and similar fish provide EPA and DHA omega-3 fatty acids. Fish can therefore reasonably be included in a mental-health-supportive dietary pattern, although it should not be presented as a treatment for depression by itself.

7. Extra-virgin olive oil. This is the principal added fat in Mediterranean-style diets and supplies monounsaturated fats and polyphenols. Evidence is stronger for the Mediterranean pattern as a whole than for olive oil independently.

8. Fermented foods. Yogurt with live cultures, kefir and some fermented vegetables can provide microorganisms and fermentation products. They're reasonable foods to include if tolerated, but current evidence does not establish that fermented foods themselves prevent or treat depression or anxiety.

What foods are associated with worse mental-health outcomes?

The clearest recent signal concerns high consumption of ultra-processed foods (UPFs).

UPFs are industrial formulations that often contain refined ingredients and additives and little intact whole food. Examples can include many soft drinks, packaged sweets, some fast foods, processed snack foods and certain highly processed ready-to-eat meals.

A 2022 systematic review involving 385,541 people found that higher UPF consumption was associated with more depressive and anxiety symptoms. Prospective studies also showed greater subsequent depression risk.

A large 2024 BMJ umbrella review similarly found higher UPF exposure associated with anxiety and depressive outcomes, although the quality of evidence for these mental-health outcomes was low.

Another 2024 meta-analysis of prospective studies found that people with high versus low UPF intake had about a 32% higher relative risk of depressive outcomes. This is an association and does not prove that UPFs caused the depression.

An important distinction for your audience

I would avoid saying:

“These foods cause depression:” sugar, fast food, soda, processed foods.

The research doesn't establish that so simply.

A more evidence-based message is:

Dietary patterns rich in minimally processed plant foods, whole grains, legumes, nuts, olive oil and fish—particularly Mediterranean-style patterns—are associated with better mental health and may help reduce depressive symptoms. Diets high in ultra-processed foods are associated with greater risk of depression and possibly anxiety.

There can also be reverse causation: depression can affect appetite, motivation, sleep, cooking and food choices. Therefore, diet may influence mental health while mental health simultaneously influences diet.

References

Abukmail, E., Pradeep, N. K., Ahmed, S., & Albarqouni, L. (2025). Moderate- to long-term effect of dietary interventions for depression and anxiety: A systematic review and meta-analysis. Annals of Internal Medicine, 178(7), 987–999. https://doi.org/10.7326/ANNALS-24-03016

Bizzozero-Peroni, B., Martínez-Vizcaíno, V., Fernández-Rodríguez, R., Jiménez-López, E., Núñez de Arenas-Arroyo, S., Saz-Lara, A., Díaz-Goñi, V., & Mesas, A. E. (2025). The impact of the Mediterranean diet on alleviating depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials. Nutrition Reviews, 83(1), 29–39. https://doi.org/10.1093/nutrit/nuad176

Lane, M. M., Gamage, E., Travica, N., Dissanayaka, T., Ashtree, D. N., Gauci, S., Lotfaliany, M., O'Neil, A., Jacka, F. N., & Marx, W. (2022). Ultra-processed food consumption and mental health: A systematic review and meta-analysis of observational studies. Nutrients, 14(13), 2568. https://doi.org/10.3390/nu14132568

Lane, M. M., Gamage, E., Du, S., Ashtree, D. N., McGuinness, A. J., Gauci, S., Baker, P., Lawrence, M., Rebholz, C. M., Srour, B., Touvier, M., Jacka, F. N., O'Neil, A., Segasby, T., & Marx, W. (2024). Ultra-processed food exposure and adverse health outcomes: Umbrella review of epidemiological meta-analyses. BMJ, 384, e077310. https://doi.org/10.1136/bmj-2023-077310

Werneck, A. O., Steele, E. M., Delpino, F. M., Lane, M. M., Marx, W., Jacka, F. N., Stubbs, B., Touvier, M., Srour, B., Louzada, M. L. C., Levy, R. B., & Monteiro, C. A. (2024). Adherence to the ultra-processed dietary pattern and risk of depressive outcomes: Findings from the NutriNet Brasil cohort study and an updated systematic review and meta-analysis. Clinical Nutrition, 43(5), 1190–1199. https://doi.org/10.1016/j.clnu.2024.03.028