Serotonin and the Gut: Where Mood Begins

When clients tell me they feel “off”—low mood, worry, poor sleep, brain fog—our conversation often moves beyond thoughts and feelings to something surprising: the gut. That may sound odd for a therapy session, but it makes sense when you learn this key fact: the vast majority of the body’s serotonin is made in the gastrointestinal tract, not the brain. In fact, reviews estimate roughly 90–95% of total serotonin is produced by specialized gut cells called enterochromaffin cells. Read more.

Serotonin is famous as a “feel-good” neurotransmitter, but in the gut it also helps move food along, calm inflammation, and talk to the nervous system that lines your intestines (the “second brain”). So when gut serotonin signaling gets out of balance, you may notice shifts in mood, stress tolerance, and even sleep, alongside digestive symptoms. Read more.

How the Gut Makes (and Shares) Serotonin

Inside your intestines, enterochromaffin cells turn the amino acid tryptophan into serotonin using an enzyme called TPH1. Most of this serotonin stays local—guiding motility, secretion, and immune activity—but it also sends signals through the vagus nerve, immune messengers, and metabolites that reach the brain. This two-way communication is called the gut–brain axis. Read more.

Here’s the part I find most fascinating: your gut microbes help control how much serotonin your gut makes. Landmark research showed that indigenous, spore-forming bacteria produce metabolites that increase serotonin biosynthesis in the colon, raising serotonin levels in the gut and blood. In germ-free animals with no microbiota, serotonin is low—until microbes or their metabolites are added back. Translation: when your microbial community shifts, your serotonin signaling can shift, too. Read more.

Why This Matters for Mental Health

From a therapist’s chair, these biology lessons become practical in three ways:

• Mood regulation is body-wide. Because most serotonin is produced peripherally (in the gut), changes in gut health can ripple into how your nervous system regulates mood, attention, and stress responses. Clinically, I see clients with longstanding digestive issues often report parallel patterns in anxiety or low mood. Reviews of gut serotonin signaling support this whole-system perspective. Read more.

• Microbial diversity supports emotional balance. A richer, more diverse microbiome is generally linked with better resilience and calmer inflammatory signaling. When diets are low in fiber, stress is high, or antibiotics are frequent, diversity may drop—potentially altering serotonin-related signaling along the gut–brain axis. Read more.

• Inflammation is a bridge. Serotonin interacts with immune pathways in the intestinal lining; when inflammation runs high, signaling can get noisy. Reviews note that potentiating or normalizing gut serotonin signaling can reduce epithelial injury and support healing—one reason I view nutrition, sleep, and stress hygiene as “therapeutic tools,” not just lifestyle tips. Read more.

Common Questions I Hear in Session

• “If most serotonin is made in the gut, do SSRIs still work?” Yes. SSRIs act primarily in the brain to affect synaptic serotonin signaling. That said, many people notice GI side effects at first because serotonin receptors are dense in the gut. Supporting the gut (gentle fiber, hydration, regular meals) often helps during medication adjustments. Read more.

• “Can food or probiotics raise my brain serotonin?” Food doesn’t deliver serotonin directly to the brain, but tryptophan-rich foods and a healthy microbiome can support your body’s overall serotonin ecosystem. The more balanced your gut, the clearer the signal along the gut–brain axis. Read more.

• “Is there proof microbes change serotonin?” Yes—mechanistic studies show gut bacteria stimulate enterochromaffin cells to produce serotonin. That’s strong biological plausibility for why gut shifts (diet, stress, antibiotics) can show up as mood shifts, too. Read more.

Therapist-Guided Ways to Support the Gut–Serotonin–Mood Loop

These are the evidence-informed practices I weave into care plans. They do not replace medical treatment; they complement it.

• Build a fiber-forward plate. Aim for colorful plants at most meals. Fermentable fibers (beans, lentils, oats, onions, garlic, apples) feed beneficial microbes that, in turn, produce metabolites influencing serotonin pathways. Even small steps—adding a half cup of beans, a piece of fruit, or a side salad—can help. (Educational overviews from medical sources emphasize food–mood links through the gut.) Read more.

• Add fermented or cultured foods (as tolerated). Yogurt, kefir, kimchi, sauerkraut, and tempeh may increase microbial diversity, which is associated with more resilient signaling. If you’re new to these foods, start with a few forkfuls or sips and notice how your gut feels. (Consumer-friendly and research-informed summaries note this direction of evidence.) Read more.

• Prioritize sleep and circadian rhythm. Your microbiome follows a daily rhythm; sleep disruption can disturb microbial balance and stress hormones that interact with serotonin. Aim for consistent bed/wake times and a dark, cool bedroom. (Neuroscience and gut-brain reviews describe this interplay.) Read more.

• Practice nervous-system regulation daily. Slow breathing, humming or singing (vagal toning), gentle movement, and spending time with safe people help calm the autonomic nervous system, the same system that carries gut–brain messages. The calmer the “line,” the clearer the signal. Read more.

• Be thoughtful with antibiotics. Use them when medically needed, but avoid unnecessary courses. If you require antibiotics, talk with your clinician about gut-supportive nutrition during and after. Microbial communities typically rebound, but care (and time) helps. (Mechanistic research shows microbes regulate gut serotonin; protecting them protects signaling.) Read more.

• Consider targeted probiotics—with guidance. Some strains (often called “psychobiotics”) have early evidence for mood and stress support, likely by modulating immune and serotonin pathways. Quality and strain specificity matter; work with a knowledgeable clinician. (Accessible medical summaries discuss emerging evidence; rigorous research is ongoing.) Read more.

A Gentle Reality Check

As exciting as this science is, we need to hold two truths:

• Truth 1: The gut produces most of the body’s serotonin, and gut microbes help regulate that production—a strong biological foundation for gut–mood links. Read more.

• Truth 2: Much of the mental-health outcome research is associational and still evolving; there isn’t a single “serotonin diet” or microbe that cures depression. We use this knowledge to add supportive levers—nutrition, sleep, nervous-system regulation—while continuing evidence-based psychotherapy and medical care. Read more.

Bringing It Into the Therapy Room

In my practice, I often map three layers with clients:

• Mind: thoughts, beliefs, emotions, meaning, relationships.

• Body: sleep, nutrition, movement, medical conditions, gut symptoms.

• Bridge: the gut–brain axis—how stress, food, and microbes shape serotonin signaling and nervous-system tone.

When a client says, “I’m anxious for no reason,” we get curious: Are meals irregular? Is fiber low? Any recent illness or antibiotics? Are there signs of gut inflammation (bloating, alternating stools, heartburn)? We don’t blame the gut for everything, but we include it—because supporting the gut often supports the mind.

Key Sources

• Most serotonin is made in the gut: Reviews estimate ~90–95% produced in the intestine by enterochromaffin cells. https://pmc.ncbi.nlm.nih.gov/articles/PMC5526216/; https://pmc.ncbi.nlm.nih.gov/articles/PMC10867509/

• Microbes regulate gut serotonin biosynthesis: Yano JM et al., Cell (2015). Open-access summary: https://pmc.ncbi.nlm.nih.gov/articles/PMC4393509/ (publisher PDF: https://www.cell.com/cell/pdf/S0092-8674(15)00248-2.pdf).

• Serotonin’s roles in gut motility, secretion, immunity: Mawe & Hoffman, Nat Rev Gastroenterol Hepatol (2013). https://pubmed.ncbi.nlm.nih.gov/23797870/

• Clinical overviews on food–mood and gut serotonin: Harvard Health explainers. https://www.health.harvard.edu/blog/gut-feelings-how-food-affects-your-mood-2018120715548; https://www.health.harvard.edu/blog/nutritional-psychiatry-your-brain-on-food-201511168626

• Gut serotonin and epithelial healing/inflammation: Shah PA et al. (2021) review. https://pmc.ncbi.nlm.nih.gov/articles/PMC8350061/https://www.health.harvard.edu/blog/gut-feelings-how-food-affects-your-mood-2018120715548