The Gut-Brain Axis: How Your Gut Bacteria Communicate with Your Brain

The gut contains more neurons than the spinal cord. That fact alone tells you this is not a simple digestive tube.

The enteric nervous system (ENS), the dense web of neurons embedded in the gut wall, operates largely on its own. It can coordinate peristalsis, secretion, and blood flow without input from the brain. But it’s also in constant dialogue with the central nervous system, and the bacteria living in the gut are participants in that conversation.

Two-Way Traffic on the Vagus Nerve

The vagus nerve is the primary physical connection between gut and brain. It’s the longest cranial nerve, running from the brainstem down through the thorax and into the abdomen, sending branches throughout the digestive tract.

What’s often misunderstood about the vagus nerve: about 80-90% of its fibers carry signals from the gut to the brain (afferent), not the other way around. The gut is primarily sending information upward, not receiving instructions downward.

Gut sensory cells called enteroendocrine cells detect what’s in the intestinal lumen: mechanical stretch, nutrient content, bacterial metabolites, and chemical signals. They relay this information through the vagus nerve to the brainstem, which integrates it into signals affecting appetite, satiety, nausea, mood, and autonomic function.

Kaelberer et al. (2018, Science) demonstrated a previously unknown gut-brain neural circuit using glutamate as a neurotransmitter at neuropod cells in the intestinal epithelium, signaling to vagal neurons within milliseconds. This is faster than hormonal signaling. The gut effectively has a high-speed line to the brain.

Gut Bacteria as Chemical Messengers

Gut bacteria don’t signal through neurons directly. They produce metabolites that interact with gut cells, which then signal the nervous and immune systems.

Short-chain fatty acids (SCFAs) are the best studied. Butyrate, propionate, and acetate (produced by bacterial fermentation of dietary fiber) activate G-protein coupled receptors on gut cells, stimulating the release of peptide YY and GLP-1 (gut hormones affecting satiety and insulin response) and potentially influencing vagal signaling. The connection between SCFAs and brain function is covered in more depth in the short-chain fatty acids guide.

Gut bacteria also produce or modulate the precursors to neurotransmitters. Tryptophan metabolism is a key example. Dietary tryptophan can be converted by gut bacteria to various downstream metabolites including indoles, kynurenine, and serotonin. The balance of these pathways appears to influence both gut and brain function.

Serotonin: Made in the Gut

About 90-95% of the body’s serotonin is produced in the gut, primarily by enterochromaffin cells in the intestinal epithelium. This is often cited as evidence that gut health directly affects mood. The relationship is more complicated.

Gut-produced serotonin cannot cross the blood-brain barrier. It doesn’t affect mood directly by traveling from the gut to the brain. Its primary role in the gut is regulating intestinal motility and secretion, and it also acts as a vagal signal.

However, gut bacteria do influence serotonin production in the gut in ways that have downstream effects. Yano et al. (2015, Cell) showed that specific gut bacteria, particularly spore-forming bacteria, stimulate enterochromaffin cells to produce serotonin. Germ-free mice had significantly lower gut serotonin levels. This matters for gut motility and for serotonin-related gut disorders.

The brain makes its own serotonin from dietary tryptophan. Gut bacteria that metabolize tryptophan through certain pathways reduce the amount available for brain serotonin synthesis. Conversely, gut bacteria that convert tryptophan toward indole-3-propionic acid pathways may support gut barrier function and reduce neuroinflammation (Cryan et al., 2019, Physiological Reviews).

The connection is real and biologically plausible, but “90% of serotonin is in the gut, therefore gut health directly affects your mood” is an oversimplification.

Immune Signaling: The Third Channel

The gut houses a large fraction of the body’s immune cells. Gut bacteria continuously interact with these immune cells, calibrating inflammatory tone. In a dysbiotic gut (one with disrupted bacterial communities), immune activation can be higher, generating systemic inflammatory signals including cytokines that cross into the brain.

Brain inflammation is associated with depression. This is the neuroimmune pathway. Pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) produced peripherally can cross the blood-brain barrier at high concentrations or signal through the vagus nerve to alter brain function. They affect the availability of tryptophan (pushing it toward the kynurenine pathway instead of serotonin) and reduce the firing rate of certain neural circuits.

The mechanistic chain is: gut dysbiosis promotes intestinal permeability, which promotes systemic immune activation, which promotes neuroimmune signaling, which affects mood and cognition. Each step has supporting evidence. The full chain in humans, from specific dietary change to measurable mood improvement, is harder to demonstrate with current tools.

What the Evidence Says About Diet

The microbiome is shaped by what you eat, as Sonnenburg and Backhed (2016, Nature) documented in their review of diet-microbiota interactions. Dietary fiber feeds the bacteria that produce SCFAs. Diverse plant food intake correlates with greater microbiome diversity. Ultra-processed food diets correlate with lower diversity and higher inflammatory markers.

Whether specific probiotic strains reliably change mood outcomes in healthy adults is a different and harder question. The clinical trial results are inconsistent, effect sizes are modest, and most studies are short and small.

The most evidence-supported dietary approach for supporting gut-brain axis health is the same one that supports general microbiome health: high variety of fiber-containing plant foods, fermented foods, and lower intake of ultra-processed foods.

This article is for educational purposes only. It’s not medical advice. Talk to your doctor or a registered dietitian before making significant changes to your diet.