In this episode, we detail the gut’s intricate immune defenses, emphasizing the role of mast cells in inflammation and immune signaling. We extend this conversation to Mast Cell Activation Syndrome briefly going through potential triggers, tests, and symptoms. Finally, we examine the bidirectional relationship between MCAS and Small Intestinal Bacterial Overgrowth (SIBO), illustrating how mast cell mediators and microbial byproducts can drive a cycle of chronic inflammation and increased intestinal permeability.

Topics:

1. Introduction to the Gut-Immune Axis

- Focus: mast cells, small intestinal bacterial overgrowth (SIBO), and mast cell activation syndrome (MCAS).

2. Anatomy of the Gastrointestinal Lining

- Intestinal lumen, microbiome, mucus layer, epithelial monolayer, tight junctions, and lamina propria.

- Role of the smooth muscle and deeper layers supporting the mucosal structures.

3. Gut-Associated Lymphoid Tissue (GALT)

- Peyer’s patches, mesenteric lymph nodes (MLNs), isolated lymphoid follicles (ILFs), intraepithelial lymphocytes (IELs), and dispersed immune cells in the lamina propria.

- Function of GALT.

4. Peyer’s Patches and Antigen Exposure

- Location and function of Peyer’s patches.

- Role in antigen sampling and processing.

5. Immune Cells in the Lamina Propria

- Overview of interspersed immune cell populations.

6. Focus on Mast Cells

- Key roles of mast cells in the gut’s innate immune system.

- Locations with a focus on the lamina propria.

7. Mast Cell Mediators

- Histamine

- Tryptase: tissue remodeling, impact on intestinal permeability.

- Cytokines, prostaglandins, and leukotrienes.

8. Mast Cell Activation Syndrome (MCAS)

- Overactivation of mast cells and excessive release of inflammatory mediators.

- Effects on gut barrier function.

- Pathological behavior due to altered activation thresholds, receptor expression, and tissue environment changes (not resulting from an increased number of mast cells).

9. MCAS Symptoms and Systemic Effects

- Abdominal pain, cramping, bloating, diarrhea, and nausea.

- Systemic symptoms: skin reactions, respiratory and cardiovascular effects, neurological impacts.

10. Triggers and Conditions Associated with MCAS

- Environmental toxins, infections, stress, chemical exposures.

- Hypermobile Ehlers-Danlos syndrome (hEDS), dysautonomia (e.g., POTS).

11. MCAS Testing

- Testing limitations: variability in mediator release and transient nature of mast cell degranulation.

- Serum tryptase, urinary N-methylhistamine, plasma heparin levels, specific cytokines like IL-6, and more.

12. Small Intestinal Bacterial Overgrowth (SIBO)

- Overview of SIBO.

- Slow motility, low stomach acid.

13. Interaction Between SIBO and Mast Cells

- SIBO-induced mast cell activation.

- Cycle of inflammation, increased intestinal permeability, and gut dysfunction.

14. Conclusion

- Recap of the intestinal anatomy and immune cell focus.

- MCAS triggers, symptoms, and testing.

- Connections between SIBO and MCAS, emphasizing an inflammatory cycle.

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