Supporting Serotonin Production: Overview
Dysbiosis, characterized by an overgrowth of pathogenic bacteria and loss of beneficial species, can disrupt serotonin synthesis within enterochromaffin cells of the intestinal lining. Serotonin is a neurotransmitter—often called the “feel-good” chemical—that plays critical roles in regulating mood, sleep, appetite, digestion, cognition, and more. We will go through how serotonin is synthesized within the intestines, how the intestinal microbiome impacts synthesis, how certain probiotics can support serotonin production both in and outside of the gut (such as through the modification of key enzymes), and we will finish the conversation by going through an absolutely remarkable tool for supporting serotonin levels via supporting the intestinal microbiome.
Serotonin Production Overview
The gastrointestinal (GI) tract is lined by a specialized group of cells, including enterochromaffin cells (EC cells), which are the primary producers of serotonin in the body. These EC cells belong to a larger class called enteroendocrine cells, which function as hormone-secreting cells within the gut. EC cells are found in the mucosal layer of the gut lining, which serves as the first barrier between the external environment in the gut lumen and the internal bodily environment. The mucosal layer itself comprises three parts: the epithelial layer, lamina propria, and muscularis mucosa. The epithelial layer consists of a single layer of tightly connected cells that both absorb nutrients and act as a selective barrier against pathogens. Interspersed within this epithelial layer, EC cells monitor the gut environment, releasing serotonin in response to specific signals such as the presence of food, gut stretch, or microbial signals. The release of serotonin from EC cells is crucial for regulating gut motility, fluid secretion, and communication along the gut-brain axis, influencing both local and systemic physiology.
Serotonin Synthesis & Signaling
The synthesis of serotonin within EC cells starts with tryptophan, an essential amino acid obtained from protein-rich foods. After ingestion, tryptophan is absorbed by cells lining the gut and transported into EC cells through specific amino acid transporters like B^0AT1 and LAT1. These transporters are located on cell membranes and use sodium ions to facilitate tryptophan’s entry. Once inside the EC cell, tryptophan undergoes two key enzymatic reactions to form serotonin. The first step is catalyzed by tryptophan hydroxylase 1 (TPH1), an enzyme that adds a hydroxyl group to tryptophan, converting it into 5-hydroxytryptophan (5-HTP). TPH1 is the rate-limiting enzyme of serotonin synthesis, meaning it controls the overall rate of serotonin production based on the availability of tryptophan and cofactors like tetrahydrobiopterin (BH4) and molecular oxygen.
In the second enzymatic step, 5-HTP is converted into serotonin by aromatic L-amino acid decarboxylase (AADC), an enzyme that removes a carboxyl group from 5-HTP, yielding the final product, serotonin (5-hydroxytryptamine or 5-HT). Once synthesized, serotonin can either be stored in vesicles within EC cells for controlled release and action on nearby cells. Vesicular storage of serotonin is facilitated by the vesicular monoamine transporter 1 (VMAT1), which packages serotonin into vesicles within EC cells, allowing for a rapid release upon stimulation. The release of serotonin occurs in response to various cues, including physical stretch of the gut wall from food intake, chemical signals, or microbial metabolites.
Upon release, serotonin acts on various serotonin receptors located in the gut lining and surrounding smooth muscle. Key receptors include the 5-HT3 and 5-HT4 receptors, which are distributed on neurons and muscle cells within the enteric nervous system, the network of neurons in the gut. Activation of these receptors influences gut motility by either speeding up or slowing down peristalsis (the wave-like contractions that move food along the digestive tract) and also affects secretion of digestive fluids. Through these actions, serotonin helps regulate gut sensations and movements, contributing to overall gut function. Additionally, serotonin produced in the gut sends signals to the central nervous system (CNS) through the vagus nerve and other pathways, linking gut activity with brain signaling. In more detail, gut-derived serotonin impacts the brain indirectly through the gut-brain axis, particularly via the vagus nerve and immune signaling pathways. These pathways allow the gut to communicate with the central nervous system by transmitting signals that influence mood, stress responses, and cognitive functions.
How Intestinal Dysbiosis Can Impact Serotonin Production:
Dysbiosis refers to an imbalance in the gut microbiota, where the composition and function of microbial communities deviate from a healthy state. In a state of dysbiosis, there is often a loss of beneficial bacteria (such as Lactobacillus and Bifidobacterium) and a proliferation of opportunistic or pathogenic bacteria.
Intestinal dysbiosis has been shown to disrupt serotonin production primarily by impacting microbial metabolite production, immune regulation, and tryptophan metabolism. In a healthy gut, certain beneficial bacteria produce short-chain fatty acids (SCFAs) like butyrate, which can positively influence the expression of tryptophan hydroxylase 1 (TPH1)—the a rate-limiting enzyme responsible for converting tryptophan into serotonin in enterochromaffin (EC) cells. Studies suggest that SCFAs may help maintain the gut environment in a way that supports TPH1 function. Dysbiosis, however, often leads to reduced SCFA production due to a decline in fiber-fermenting bacteria, which can limit TPH1 expression and, consequently, serotonin synthesis.
Dysbiosis can also contribute and lead to intestinal inflammation. In other words, the presence of pathogenic bacteria or a lack of beneficial bacteria can trigger immune responses that lead to inflammation within the gut lining, and these cytokines and other inflammatory molecules can affect EC cell function and can disrupt serotonin production. Additionally, dysbiosis can also influence the metabolism of tryptophan, the precursor to serotonin.
Lactobacillus plantarum DR7 and The Brain, Case Study: When it comes to analyzing stress and serotonin, we can also examine serotonin production that occurs directly in the central nervous system. TPH2, primarily expressed in the brain, plays a central role in converting tryptophan to serotonin specifically in neural tissue, while TPH1 is more widely expressed across the brain, gastrointestinal tract, and pituitary glands. There was a remarkable, randomised, double-blind, placebo-controlled study detailing the effects of administration of Lactobacillus plantarum DR7 on TPH2 expression and stress, and they documented a 3.7-fold increase in blood TPH2 expression compared to the placebo - truly incredible findings!
Therefore, How Can We Support Serotonin Production in the Intestines as Well as Outside of the Intestines?
Bacteriophages
Bacteriophages, such as LH01 (Myoviridae), LL5 (Siphoviridae), T4D (Myoviridae), and LL12 (Myoviridae), can specifically target certain pathogenic bacterial strains helping to restore microbial balance and creating conditions that favor serotonin synthesis by beneficial bacteria. In more detail, these phages may attach to bacterial cells, inject their genetic material, and use the bacterial machinery to reproduce. As the phages replicate, they eventually can cause the bacterial cell to burst (lyse), releasing new phages.
Probiotics
Probiotics can support serotonin production by fostering a balanced gut microbiome, creating optimal conditions for enterochromaffin (EC) cells in the gut to synthesize serotonin. Additionally, remarkable probiotics such as Lactobacillus plantarum DR7 can support various pathways contributing to the conversion of tryptophan into serotonin within neural tissue.
Nouri Stress & Hormone Balance Probiotics with Prebiotics
All of these (LH01 (Myoviridae), LL5 (Siphoviridae), T4D (Myoviridae), LL12 (Myoviridae), and Lactobacillus plantarum DR7) are formulated within Nouri Stress Probiotic with Prebiotics. It combines an array of remarkable probiotics, including Lactobacillus plantarum DR7®, Levilactobacillus brevis KABP™-052, and Lactiplantibacillus plantarum KABP™-023; and it was expertly designed to support both intestinal health, mood, and serotonin production. Daily Nouri also utilizes capsule-in-capsule technology designed to facilitate remarkable probiotic delivery directly to the gut.
They recommend taking one capsule per day, with or without food, to support your gut microbiome and mitigate stress-related digestive upset.
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*Always consult with a licensed medical professional for all of your medical needs and before taking any nutritional supplement.
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