Your Gut Is Not Like Las Vegas, Part 4: Depression, Anxiety and the Gut-Brain Axis

By Adrian Stone, BHSc (Nutritional Medicine), BHSc (Naturopathy), Living Holistic Health — The gut-brain axis and depression: what the largest human studies show, the Geelong trial in which changing the diet changed the mood, and what not to buy.

Your Gut Is Not Like Las Vegas · Part 4 of 5 · Part 1 · Part 2 · Part 3

If there is one condition where the gut–brain axis has moved from hypothesis to human evidence, it is depression. The microbiome studies are the largest in this series. There is a randomised trial — run here in Geelong — in which changing the diet changed the depression. And there is a rat experiment whose design is hard to argue with.

Before any of that: if you are in a bad place right now, this article can wait. Lifeline is 13 11 14, any hour, and 000 if you are in danger. If you are on an antidepressant, nothing below is a reason to change it. The gut work in this piece sits alongside your GP, psychologist or psychiatrist — never instead of them.

The rule from Part 1 holds for the gut-brain axis and depression too: association is not cause. But depression is the condition where the arrow has been tested in both directions. That is what makes it worth an article of its own.

Is the Gut Microbiome Different in People with Depression?

Yes, and the pattern is consistent across diagnoses. A 2021 meta-analysis pooled 59 studies of adults with depression, bipolar disorder, psychosis, anxiety and other conditions. The same signature appeared across diagnoses: fewer of the butyrate-producing bacteria Faecalibacterium and Coprococcus, and more of the pro-inflammatory genus Eggerthella.

Two things about that finding matter more than the bacterial names. First, it was transdiagnostic — the microbiome did not distinguish depression from anxiety from bipolar disorder. It distinguished psychiatric illness from health. That argues against a “depression microbiome” and for a general state of gut inflammation that travels with a struggling brain. Second, the depleted organisms are the same butyrate makers that have run low in every part of this series. The gut, it seems, has one main way of being unwell, and many conditions share it.

One of the largest population studies says the same thing from a different angle. The Flemish Gut Flora Project studied 1,054 people and validated its findings in another 1,070. The butyrate producers Faecalibacterium and Coprococcus tracked with higher quality-of-life scores. Coprococcus and Dialister were depleted in people with depression, even after accounting for antidepressant use. That last clause is the important one. Antidepressants change the gut too, and the association survived the correction.

Does the Gut-brain Axis Cause Depression, or Does Depression Change the Gut?

Both directions have evidence, and the honest answer is that they feed each other. A 2016 experiment transferred gut bacteria from people with depression into rats and produced anxiety-like behaviour, anhedonia and altered tryptophan metabolism in the animals. Meanwhile, stress, poor sleep and altered eating — all part of depression — reshape the gut from the top down.

The transplant experiment

The rat study, from University College Cork, is small and it is in rats, so hold it loosely. The researchers compared the gut bacteria of 34 people with major depression and 33 matched controls. Then they took stool from a subgroup of each and transferred it into rats whose own microbiome had been cleared. The rats that received the “depressed” microbiome developed anhedonia-like and anxiety-like behaviour and a shift in tryptophan metabolism; the ones that received the control microbiome did not. Something in the bacteria was carrying part of the phenotype.

How the gut talks to the brain

A 2019 overview from the same Cork group lays out the roads. The vagus nerve, running from gut to brainstem, carries far more traffic upward than downward. The immune system reads the gut wall constantly and signals inflammation to the brain. Gut bacteria influence how tryptophan, the raw material for serotonin, is metabolised. Roughly ninety per cent of the body’s serotonin is made in the gut lining — though that serotonin stays in the gut, running motility and immune signalling; it does not reach the brain. And the short-chain fatty acids the butyrate producers make cross into the blood and calm immune cells. None of these is exotic. All of them are measurable.

Is Depression an Inflammatory Condition?

In about a quarter of people with depression, yes. That group carries low-grade inflammation, a C-reactive protein above 3 mg/L, according to a 2019 meta-analysis of 37 studies and more than 13,000 patients. Not all depression is inflammatory. Where it is, the gut is, in my view, the most plausible source and the one most open to change.

This is chronic inflammation, one of the four root drivers I see across almost every case, showing up in the brain.

Can Changing What You Eat Change Depression?

Yes — that is the finding of the trial I would put in front of every patient. SMILES, run from Deakin University in Geelong, randomised 67 adults with moderate to severe depression to twelve weeks of dietary support or social support. The diet group’s depression scores fell substantially more, and 32% reached remission against 8% of the controls.

The SMILES trial is worth knowing properly, because it is small and it is local and it is honest about both. Sixty-seven people is not many. The intervention, seven sessions with a clinical dietitian moving people toward a Mediterranean-style pattern, could not be blinded. The control condition, social support, was chosen to match the attention the diet group received, which is better than most nutrition trials manage. On the primary outcome, the difference was large (an effect size of about 1.2), and the number needed to treat for remission was four. Everyone in the trial stayed on whatever treatment they were already receiving. This was alongside care, not instead of it — which is exactly the frame we work in.

Nobody should read SMILES as “diet cures depression”. Read it this way. In a randomised trial, changing what people ate, while their other treatment continued, moved the needle more than the same amount of attention without the diet. That is a strong claim, and it is one the trial supports.

What About Probiotics for Depression?

The signal is real but modest, and it depends on how you slice the trials. A 2026 network meta-analysis of gut-targeted interventions in major depression found they reduced symptoms overall, with microbiota-based therapies ranking best at low-to-moderate certainty. As a standalone treatment, the pooled effect did not reach significance.

That last point is the one the marketing leaves out. In the network analysis, gut-targeted interventions were also tested as monotherapy, the only condition that removes the confounding of antidepressants. There, the effect was small and its confidence interval crossed zero. As an add-on to usual care, there was a benefit. A 2026 meta-analysis of short-chain fatty acid interventions in Brain, Behavior, and Immunity reached a similar place. Preliminary evidence of benefit, with a hint that body weight may change the response. That is a research agenda, and a promising one. It is not a reason to buy a capsule instead of seeing your doctor.

My position is the same as in Part 1. Diet first, because that is where the strongest human evidence sits. Whether a specific strain adds anything on top of a good diet is an open question. The trials that would settle it are only now being designed properly.

What Does Gut Work for Depression Look Like in Practice?

It looks like the unglamorous basics, done consistently, alongside whatever treatment you already have. That is where the gut-brain axis and depression evidence actually lands. Fibre from vegetables, legumes and whole grains to feed the butyrate producers. Fewer ultra-processed foods. Regular meals. Sleep protected. Movement most days. And digestive symptoms taken seriously rather than absorbed into “just how I am”.

In my clinic, a first appointment for someone whose mood and gut have both been off starts with the timeline. Which came first? What changed around the time things shifted? What makes each better or worse? Then a proper diet history — the actual pattern, not the intended one. Then a read of the bloods already done, with particular attention to iron, B12, vitamin D and thyroid function. Each of those can drag mood on its own. The stress load gets its own conversation. If the body is stressed, it cannot properly heal, and a nervous system stuck in fight-or-flight does not digest well either.

Does anyone need a stool test? My rule is unchanged: only if it would better inform the plan and get you a better result faster. For mood, the history and the bloods tell me most of what I need. Where a gut test earns its place is persistent digestive symptoms that the basics have not shifted.

Where Does a Naturopath Fit Alongside a GP or Psychologist in Depression?

Next to them, in our own lane. We don’t diagnose or treat depression or anxiety; that stays with your doctor, psychologist or psychiatrist. Our part is the nutritional, herbal and lifestyle work that sits alongside their care. That means the diet, the gut, the nutrient gaps, the sleep and the stress load that a medication review doesn’t have room for.

Nothing in this article is a reason to change or stop an antidepressant. If you are thinking about that, the conversation belongs with the prescriber. What we add is the terrain: a gut that is fed and moving, a plate with a randomised trial behind it, and a body under less strain.

What’s Next in This Series?

Part 5 closes the series with autoimmunity beyond MS: rheumatoid arthritis, thyroid disease, lupus and type 1 diabetes, and the one gut pattern that runs through all of them. Four organs, four specialists, one plate. Same rule as every part. Your gut is not like Las Vegas.

Positive change means sacrifice. In depression the hardest sacrifice is often the comfort of a single explanation: “it’s my gut”, “it’s my serotonin”, “it’s just me”. The evidence says it is several things at once, and that the plate is one of the few you can change tomorrow.

If you’re in Geelong or on the Bellarine and want the nutritional side of this looked at properly, the first appointment is where we start. Alongside your GP or psychologist, never instead.

Book an appointment

Frequently Asked Questions

Can gut bacteria cause depression?

In animals, transferring the gut bacteria of people with depression produces depression-like behaviour, and in humans the microbiome is consistently different in depression. But the human evidence is association, and depression itself changes the gut through stress, sleep and eating. The best reading is that the two feed each other, not that one causes the other.

Does diet help depression?

The SMILES trial, run in Geelong, randomised adults with moderate to severe depression to dietary support or social support alongside their usual treatment. The diet group improved more, and remission was 32% versus 8%. It is a small trial, but it is randomised, and it supports diet as a genuine adjunct to standard care — not a replacement.

Should I take a probiotic for depression?

The pooled evidence shows a modest benefit as an add-on to usual care, at low-to-moderate certainty, and no clear benefit as a standalone treatment. Diet has the stronger evidence. Speak with your GP before adding anything, and never stop an antidepressant to try one.

Who should I talk to first?

Your GP. If you are in crisis, Lifeline is 13 11 14. A naturopath works alongside your GP, psychologist or psychiatrist on the diet, gut, nutrient and lifestyle side — never as the first or only port of call.

References

Research located via PubMed. All links go to the original papers.

1. Nikolova VL, Smith MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Perturbations in gut microbiota composition in psychiatric disorders: a review and meta-analysis. JAMA Psychiatry. 2021;78(12):1343-1354. https://doi.org/10.1001/jamapsychiatry.2021.2573
2. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4(4):623-632. https://doi.org/10.1038/s41564-018-0337-x
3. Kelly JR, Borre Y, O’Brien C, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109-118. https://doi.org/10.1016/j.jpsychires.2016.07.019
4. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877-2013. https://doi.org/10.1152/physrev.00018.2018
5. Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019;49(12):1958-1970. https://doi.org/10.1017/S0033291719001454
6. Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017;15:23. https://doi.org/10.1186/s12916-017-0791-y
7. Jin Y, et al. Efficacy of gut microbiota-targeted interventions for major depressive disorder: a systematic review and network meta-analysis. Nutr Rev. 2026. https://doi.org/10.1093/nutrit/nuag117
8. Tang Y, et al. A systematic review and meta-analysis of the therapeutic role of short-chain fatty acids in modulating depressive symptoms. Brain Behav Immun. 2026;106987. https://doi.org/10.1016/j.bbi.2026.106987

This article is general information only and is not a substitute for individual medical advice. If you are experiencing depression or anxiety, please speak with your GP; in a crisis, call Lifeline on 13 11 14. Do not start, stop or change any medication on the basis of this article. For private health consultation claiming, please enquire with your health fund to assess coverage. Nutrition consultations are covered by some private health funds — please check with yours first.

Adrian Stone

Adrian is a qualified Nutritionist specialising in Digestive Complaints, Autoimmune Diseases, Food Intolerances, Alzheimer’s Disease and Chronic Fatigue. Book an appointment with Adrian. Ph: 03 5201 0557