The Synthesis of Wellness

153. The Role of the Intestinal Microbiome in Modulating HPA Axis Activity | Intestinal Barrier Function, Cortisol, Testing, & More

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In this episode, we dive into the interplay between the hypothalamic-pituitary-adrenal (HPA) axis and the microbiota-gut-brain (MGB) axis, highlighting their bidirectional communication through endocrine, immune, and neural pathways. We’ll explore how gut-derived metabolites like short-chain fatty acids (SCFAs) and endotoxins like LPS influence HPA axis activity; conversely, we explore how dysregulated cortisol can impact gut barrier function, immune signaling, and more. We also discuss testing including stool analysis and DUTCH tests.


Topics:

  • 1. HPA Axis and MGB Axis Interaction

    • The HPA axis and microbiota-gut-brain (MGB) axis are bidirectionally connected.
    • Gut microbiota influences the HPA axis via metabolites and more

    • 2. Overview of the HPA Axis and Cortisol Secretion

      • Stress signals activate the hypothalamus to release CRH.
      • Stimulates the anterior pituitary to produce ACTH.
      • ACTH signals the adrenal cortex.
      • The adrenal cortex releases cortisol, which binds to glucocorticoid receptors (GRs).

      • 3. Cortisol Dysregulation Impact on Intestinal Health

        • Intestinal lining anatomy: epithelial cells
        • Tight junction proteins regulate nutrient trafficking and prevent pathogen entry.
        • The mucosa contains epithelial cells, connective tissue (lamina propria), and a thin muscle layer.

        • 4. Glucocorticoid Receptors (GRs) in the Gut

          • GRs are intracellular receptors that modulate gene expression when activated.
          • Cortisol binding causes GRs to translocate to the nucleus and bind DNA at GREs.
          • GRs on epithelial cells.
          • Modified tight junction protein expression.

          • 5. Gut Microbiome's Role in HPA Axis Activity

            • SCFAs, including acetate, propionate, and butyrate, produced by gut bacteria fermenting dietary fiber.
            • SCFAs support gut integrity, reduce inflammation, and act as signaling molecules.
            • A diverse and healthy microbiome can enhances HPA regulation via SCFAs.

            • 6. SCFA Modulation of the HPA Axis

              • SCFAs and cortisol.
              • Research highlights SCFAs’ ability to attenuate stress-induced cortisol increases.

              • 7. Dysbiosis - Impact on the HPA Axis

                • Dysbiosis reduces SCFA production, impairing gut barrier integrity and immune signaling.
                • Dysbiosis, intestinal hyperpermeability and LPS.
                • LPS activates inflammatory pathways.

                • 8. Inflammation and Dysregulated HPA Activity

                  • Chronic inflammation and cortisol.
                  • Inflammatory signals from the gut exacerbate systemic and neural stress responses.

                  • 9. Symptoms of HPA Axis Dysfunction

                    • Chronic fatigue, disrupted sleep, mood disturbances...

                    • 10. Identifying Root Causes

                      • Dysbiosis, chonic infection / chronic inflammation...
                      • DUTCH Test
                      • Stool analysis



                        • Thanks for tuning in!

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                        The Synthesis of WellnessBy Chloe Porter
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