The Human Biome · Article 2 of 26
Anatomy and Physiology of the Gut–Brain Communication System
Educational and scope notice
This material is for education only and does not provide medical diagnosis or treatment advice. IEMT practitioners should remain within their professional scope and refer clients to an appropriately qualified healthcare professional where medical assessment, treatment, prescribed medication, supplements or restrictive diets are involved.
The gut–brain axis functions through an intricate network of neural, hormonal, metabolic, and immune pathways that together maintain physiological and psychological homeostasis. This module examines the key anatomical and biochemical systems involved in this bidirectional communication and explains how these systems contribute to emotional regulation, stress response, and overall well-being.
Enteric Nervous System (ENS): Structure, Autonomy, and Interaction with the CNS
The enteric nervous system (ENS) is an extensive and highly specialised network of neurones embedded within the walls of the gastrointestinal tract, stretching from the oesophagus to the rectum. Comprising approximately 100 million neurones: more than in the spinal cord (Furness, 2012), the ENS is capable of autonomous sensory integration, reflex activity, and motor control, earning it the title of the body’s “second brain”.
The ENS consists primarily of two major plexuses:
- The myenteric plexus (Auerbach’s plexus)—located between the circular and longitudinal muscle layers- is responsible for regulating motility and peristalsis.
- The submucosal plexus, also known as Meissner's plexus, is located within the submucosa and regulates local secretion, absorption, and blood flow.
Location of interstitial cells of Cajal (ICCs) sub-types according to the gastrointestinal layer. ICC-SM: ICC of submucosa; ICC-DMP: ICC of deep muscle plexus; ICC-IM: ICC of intramuscular layer; ICC-MP: ICC of myenteric plexus; ICC-SS: ICC of sub-serosa.
Source: López-Pingarrón, L. et al. (2023). Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress. Curr. Issues Mol. Biol. 2023, 45, 3552-3572.
Although the ENS can operate independently of the central nervous system (CNS), it is continuously connected via both parasympathetic and sympathetic fibres. The parasympathetic branch, particularly the vagus nerve, provides inhibitory control and sensory feedback to the brain, while sympathetic fibres modulate vasoconstriction and stress-related responses. This dual influence enables a dynamic balance between gut autonomy and central regulation.
Essential vs Non-Essential Amino Acids
Amino acids are the building blocks of proteins, and they are categorised according to whether the body can produce them internally.
Essential amino acids cannot be synthesised by the body and must be obtained through the diet.
Examples: lysine, tryptophan, methionine, and phenylalanine.
Non-essential amino acids can be produced in the body by other compounds.
Examples: alanine, glutamine, and tyrosine.
Tyrosine, for instance, is non-essential because it is synthesised from phenylalanine, an essential amino acid.
Microbiome connection:
Gut bacteria influence both the absorption and synthesis of amino acids. A healthy microbiome supports balanced amino acid metabolism, which in turn affects neurotransmitter production, tissue repair, and overall mood and energy regulation.
Vagal Pathways and Afferent Signalling: Influence on the Limbic System and Emotional Regulation
The vagus nerve serves as the principal conduit for neural communication between the gut and the brain. Roughly 80%–90% of vagal fibres are afferent, transmitting sensory information from the gut to the brainstem nuclei, such as the nucleus tractus solitarius (NTS). From here, signals project to limbic and cortical structures, including the amygdala, hippocampus, and prefrontal cortex, which are central to emotional regulation and memory processing.
Through these pathways, gut activity can directly influence mood, anxiety, and affective stability. For instance, vagal afferent stimulation indirectly modulates neurotransmitter systems (including gamma-aminobutyric acid (GABA) and serotonin) through its influence on brainstem and limbic circuits involved in emotional regulation. Conversely, vagal inhibition or dysregulation (often associated with chronic stress or inflammation) may reduce emotional resilience and amplify physiological arousal.
How Serotonin Originates in the Gut
Although serotonin is best known as a neurotransmitter in the brain, approximately 90–95% of the body’s total serotonin (5-hydroxytryptamine, 5-HT) is synthesised within the gastrointestinal tract, not the central nervous system.
The process begins with the essential amino acid tryptophan, obtained exclusively through dietary sources such as eggs, poultry, fish, nuts, and seeds. Within specialised cells in the intestinal lining, known as enterochromaffin (EC) cells, tryptophan is converted into serotonin through a two-step enzymatic process:
Hydroxylation:
The enzyme tryptophan hydroxylase-1 (TPH1) adds a hydroxyl group to tryptophan, forming 5-hydroxytryptophan (5-HTP).
Decarboxylation:
The enzyme aromatic L-amino acid decarboxylase then removes a carboxyl group from 5-HTP, yielding serotonin (5-HT).
Once synthesised, serotonin is released into the gut lumen, the enteric nervous system (ENS), and the circulatory system, where it exerts multiple physiological effects:
- It regulates intestinal motility, promoting peristalsis and secretion.
- It modulates visceral sensitivity, influencing sensations such as fullness or discomfort.
- Through vagal afferents, it transmits sensory information from the gut to the brainstem, influencing mood and affective tone.
Serotonin produced in the gut does not cross the blood–brain barrier, but it indirectly affects central serotonin levels by modulating tryptophan availability and vagal signalling. Moreover, gut microbes profoundly influence this system:
- Certain bacterial species (e.g., Streptococcus, Escherichia, and Enterococcus) can metabolise tryptophan or stimulate EC cells to increase serotonin release.
- Microbial metabolites such as short-chain fatty acids (SCFAs), particularly butyrate, have been shown to increase TPH1 expression in enterochromaffin cells, enhancing serotonin synthesis (Reigstad et al., 2015).
Conversely, dysbiosis or inflammation may reduce serotonin availability, contributing to disturbances in both gut function and emotional regulation.
Thus, the gut acts as both a biochemical factory and a sensory organ for serotonin production, forming a crucial component of the microbiota–gut–brain axis that links digestion, mood, and emotional processing.
Clinical Note for IEMT Practitioners
Visceral sensations that emerge during emotional recall - such as tightness, nausea, or warmth in the abdomen - may correspond with vagal activity and afferent feedback to limbic regions. While IEMT interventions operate at the level of kinaesthetic and visual imprints, an awareness of these physiological dynamics helps practitioners contextualise the bodily responses that accompany shifts in emotional state.
Microbial Metabolites: Short-Chain Fatty Acids, Neurotransmitter Precursors, and Cytokine Modulation
Microbial metabolism within the gut generates a wide array of bioactive compounds that influence both local and systemic physiology. Among the most significant are the short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate) produced through bacterial fermentation of dietary fibre. SCFAs serve as energy substrates for colonocytes, enhance epithelial barrier integrity, and exert anti-inflammatory effects by modulating gene expression in immune cells.
Beyond SCFAs, gut microbes synthesise or influence the availability of neurotransmitter precursors such as tryptophan (for serotonin), tyrosine (for dopamine and noradrenaline), and glutamate (for GABA). These compounds can cross or signal through the intestinal–blood–brain interface, shaping neurochemical tone within the central nervous system.
Microbial activity also affects the balance of cytokines - small signalling proteins that orchestrate immune responses. A stable microbiota tends to promote the release of anti-inflammatory cytokines (e.g., interleukin-10), whereas dysbiosis favours pro-inflammatory cytokines (e.g., interleukin-6, tumour necrosis factor-α), which have been linked to mood dysregulation and cognitive decline.
Tyrosine – Precursor to Dopamine and Noradrenaline
Tyrosine is a non-essential amino acid derived from phenylalanine and is a key precursor in the synthesis of catecholamine neurotransmitters, including dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine). These neurotransmitters play vital roles in motivation, focus, stress response, and mood regulation.
Under conditions of stress, sleep deprivation, or cognitive demand, the body’s stores of catecholamines can become depleted. Supplementing with L-tyrosine has been shown to support mental performance, working memory, and resilience to stress by replenishing dopamine and noradrenaline levels in the brain.
Tyrosine availability can also be influenced by gut microbiome activity, as intestinal bacteria contribute to amino acid metabolism and absorption. Thus, gut health indirectly affects neurotransmitter balance and emotional regulation.
Key roles:
- Precursor for dopamine (motivation, reward, pleasure)
- Precursor for noradrenaline (alertness, attention, stress response)
- Supports cognitive function during stress and fatigue
- Dependent on adequate vitamin B6, copper, and iron for conversion
The Hypothalamic–Pituitary–Adrenal (HPA) Axis: Gut-Mediated Influence on Stress Response
The HPA axis is the central neuroendocrine system that governs the body’s response to stress. Activation begins in the hypothalamus with the secretion of corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH then prompts the adrenal cortex to produce cortisol: the principal stress hormone.
Source: Original concept by Jessica Malisch and Theodore Garland (2004).
HPA Axis Diagram (Brian M. Sweis, 2012). Wikimedia Commons.
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Licence: CC BY-SA 3.0.
The gut microbiota exerts regulatory influence on the HPA axis via neural, immune, and metabolic signalling. Experimental studies have demonstrated that germ-free animals exhibit exaggerated cortisol responses to stress, which normalise following microbial colonisation, suggesting that commensal bacteria play a buffering role in stress physiology (Sudo et al., 2004). Certain probiotic strains, such as Lactobacillus plantarum and Bifidobacterium longum, have been observed to attenuate HPA activation and reduce cortisol levels, supporting their potential as psychobiotic agents.
Conversely, chronic dysbiosis, intestinal permeability (“leaky gut”), or systemic inflammation can overstimulate the HPA axis, resulting in prolonged cortisol exposure, altered immune regulation, and increased vulnerability to anxiety, depression, and fatigue. Thus, gut health is both a determinant and a reflection of stress regulation capacity.
Summary
- The gut–brain axis operates through integrated neural, endocrine, immune, and metabolic pathways.
- The enteric nervous system functions as a semi-autonomous neural network capable of direct communication with the central nervous system.
- Vagal afferent signalling links gut activity to emotional regulation via limbic and cortical circuits. (Porges, 2011)
- Microbial metabolites and cytokines modulate neurochemical balance and inflammatory tone.
- The HPA axis provides a hormonal interface between psychological stress and gut function, influenced by microbial activity.
Reflective Questions
- How might awareness of ENS and vagal signalling inform your interpretation of kinaesthetic responses during IEMT sessions?
- What indicators might suggest that chronic stress or dysbiosis is influencing a client’s emotional presentation?
- How can practitioners discuss gut–brain mechanisms responsibly without entering the domain of medical treatment?
Suggested Reading
- Mayer, E. A., Tillisch, K., & Gupta, A. (2015). Gut/brain axis and the microbiota. Journal of Clinical Investigation, 125(3), 926–938.
- Bravo, J. A., Forsythe, P., Chew, M. V., et al. (2011). Ingestion of Lactobacillus rhamnosus regulates emotional behaviour and central GABA receptor expression via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050–16055.
- de Weerth, C. (2020). Do bacteria shape our development? Crosstalk between intestinal microbiota and the HPA axis. Neuroscience & Biobehavioral Reviews, 113, 563–581.
- Furness, J. B. (2012). The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9, 286–294 (2012).
- Reigstad, C. S., Salmonson, C. E., et al. (2015). Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB Journal, 29(4), 1395–1403.
- Porges, S. W. (2011). The polyvagal theory: Neurophysiological foundations of emotions, attachment, communication, and self-regulation. W. W. Norton & Company.
- Sudo, N., et al. (2004). Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. Journal of Physiology, 558(1), 263–275.