You've felt it before: the stomach-clenching anxiety before an important event, the "butterflies" of excitement, the gut feeling (literal) that something is wrong. Most people interpret these as the brain signaling the gut — emotions producing physical symptoms. But the neuroscience of the last decade has revealed that the communication runs in both directions — and the gut may be doing more of the talking than we realized.
The gut-brain axis is one of the most active areas of research in both neuroscience and nutrition science. What it's revealing has significant implications for how we think about mental health, mood, and the relationship between what we eat and how we feel.
The Gut as a Second Brain
The enteric nervous system — the complex network of neurons lining the gastrointestinal tract — contains roughly 500 million neurons. That's more than the spinal cord. It can function independently, regulating digestion, peristalsis, and local immune responses without input from the brain.
The vagus nerve is the main highway between the gut and the brain. Critically: about 80–90% of the fibers in the vagus nerve run from the gut to the brain, not the other way around. Your gut is sending constant signals upward about the state of your digestive environment — information about what you've eaten, what's being digested, what microorganisms are present, and what immune responses are active.
The brain interprets these signals. The resulting influence on mood, anxiety, and cognition is what researchers are working to characterize.
The Microbiome: A Community With Outsized Influence
The human gut hosts approximately 39 trillion microbial cells — roughly the same number as the human cells in your body. This community of bacteria, fungi, and viruses (the microbiome) is metabolically active in ways that directly affect brain function.
Neurotransmitter production: Roughly 90–95% of the body's serotonin — a neurotransmitter critically involved in mood regulation — is produced in the gut, not the brain. It doesn't cross the blood-brain barrier in meaningful quantities (so gut serotonin doesn't directly mediate your mood the way SSRIs do), but it's involved in gut-brain signaling and in local enteric nervous system function. Gut bacteria also influence the production of GABA, dopamine precursors, and short-chain fatty acids that have neuroactive properties.
The immune-inflammation pathway: The microbiome plays a central role in regulating immune activity. Dysbiosis — an imbalanced microbial community — is associated with increased gut permeability ("leaky gut") and elevated systemic inflammation. Chronic low-grade inflammation is now one of the most studied mechanisms linking diet, gut health, and psychiatric conditions including depression and anxiety. Multiple large studies have found elevated inflammatory markers in people with major depression.
The HPA axis regulation: The microbiome influences how the HPA axis — the body's central stress response system — is calibrated. Animal studies (including the landmark germ-free mouse experiments) show that mice raised without any gut microbiome have exaggerated stress responses and altered anxiety behaviors. Reintroducing specific bacterial strains can normalize these responses.
What the Human Research Shows
The animal research on gut-brain connections is striking. The human research is more limited, more nuanced, but increasingly compelling.
The Mediterranean diet and depression: Multiple large observational studies and several randomized trials (including the SMILES trial, 2017) have found that the Mediterranean diet — high in vegetables, legumes, fish, olive oil, and whole grains, low in processed food and refined sugar — is associated with lower rates of depression and anxiety. The SMILES trial specifically found that dietary intervention improved depression scores comparably to social support therapy.
Psychobiotics: A small but growing body of research examines whether specific probiotic strains or prebiotic fiber supplementation can improve mood and anxiety. Results are mixed and effect sizes are modest, but several strains (Lactobacillus rhamnosus, Bifidobacterium longum) have shown measurable reductions in anxiety-related behaviors in humans.
Fermented foods: A 2021 Stanford study found that a diet high in fermented foods (yogurt, kefir, kimchi, sauerkraut, kombucha) increased microbiome diversity and decreased markers of inflammation over a 10-week period, compared to a high-fiber diet. Microbiome diversity is generally considered a marker of gut health and resilience.
Ultra-processed food and mental health: Cross-sectional and longitudinal studies consistently find associations between high ultra-processed food consumption and increased rates of depression, anxiety, and cognitive decline. The mechanisms likely include both direct effects (additives, emulsifiers, sugar) and indirect effects via microbiome disruption and inflammation.
What Good Gut Health Looks Like Dietarily
The dietary patterns associated with microbiome diversity and gut-brain health in the current evidence:
Diversity of plant foods: Research suggests eating 30+ different plant foods per week (not 30 portions — 30 different types) is associated with significantly higher microbiome diversity. This includes fruits, vegetables, whole grains, legumes, nuts, seeds, and herbs. Variety matters as much as quantity.
Fiber: Gut bacteria ferment dietary fiber, producing short-chain fatty acids (SCFAs) — particularly butyrate — that feed gut lining cells, reduce inflammation, and appear to have direct effects on brain function via the vagus nerve. Most people in developed countries eat well below recommended fiber intakes.
Fermented foods: The live bacteria in traditional fermented foods (as opposed to pasteurized products where bacteria are killed) contribute to microbiome diversity and may have direct beneficial effects. Yogurt, kefir, tempeh, miso, and traditionally made sauerkraut and kimchi are the most accessible sources.
Reducing ultra-processed food: The additives, emulsifiers, and sugar in highly processed foods appear to disrupt the gut lining and microbial balance in ways that promote inflammation. The evidence for reducing ultra-processed intake is stronger than the evidence for any specific supplement.
Polyphenols: Plant compounds found in dark chocolate, berries, olive oil, green tea, and red wine act as prebiotics — feeding beneficial bacteria — and have anti-inflammatory properties. This is one reason the Mediterranean diet performs as well as it does in research.
The Practical Takeaway
The gut-brain connection doesn't mean your mood is entirely controlled by what you eat, or that diet is a substitute for therapy or medication in clinical mental health conditions. It does mean that the gut is a meaningful input into mental state, and that dietary choices have genuine effects on mood, anxiety, and cognitive function through mechanisms science is only beginning to map clearly.
The dietary pattern the evidence most strongly supports — diverse, plant-rich, fermented-food-inclusive, low in ultra-processed food — is also the pattern most strongly supported by cardiovascular, metabolic, and cancer risk research. These aren't competing recommendations. They're the same direction, derived from multiple angles.
Feed the microbiome well. The brain notices.