176. The Gut-Immune Axis and Small Intestinal Fungal Overgrowth | Contributing Factors to Fungal Overgrowth, and a Conversation on Mast Cell Activation Syndrome

In this episode, we discuss the gut-immune axis and Small Intestinal Fungal Overgrowth (SIFO), with a mechanistic focus on immune activation and epithelial barrier disruption. We detail contributing factors to and symptoms of SIFO. We further discuss the anatomical positioning and immunological functions of mast cells within the lamina propria, highlighting mast cell activation syndrome, while detailing how SIFO and SIBO can serve as upstream triggers for mast cell activation.

Topics:

1. The Gut-Immune Axis and Mast Cells

- The intestinal epithelium forms the innermost selective barrier, coated in a protective mucus layer.

- Immediately beneath lies the lamina propria, rich in immune cells including mast cells.

2. Mast Cells in the Lamina Propria

- Mast cells are positioned near nerves, capillaries, lymphatics, and epithelial cells within the lamina propria.

- Their anatomical location enables rapid immune surveillance and inflammatory response.

- Mast cell granules store histamine and more.

3. Mast Cell Mediators

- Histamine: Biogenic amine, inflammatory signaling.

- Tryptase: A serine protease.

- Cytokines and lipid mediators also released upon activation.

4. Mast Cell Activation Syndrome (MCAS)

- Systemic: skin, respiratory tract, cardiovascular system, nervous system, and more.

- The gastrointestinal tract.

- Common triggers for mast cell activation.

5. Transition to Small Intestinal Fungal Overgrowth (SIFO)

- Overgrowth of fungal organisms, often candida species, within the small intestine.

- Contributing factors including hypochlorhydria, slowed motility, immune suppression, disrupted bacterial populations.

- Overlap: SIFO, SIBO

6. Hypochlorhydria and the Stomach’s Defense Role

- Parietal cells secrete hydrochloric acid (HCl) and intrinsic factor.

- HCl denatures proteins and sterilizes ingested pathogens.

- Chief cells secrete pepsinogen, which becomes pepsin in acidic conditions to digest proteins.

- Consequences of Reduced Gastric Acidity

7. The Role of Intestinal Motility

- Enteric nervous system (ENS), myenteric and submucosal plexuses.

- Coordinated contractions preventing stasis and microbial overgrowth.

8. Common Symptoms of SIFO and clinical overlap with SIBO

9. Candida and Fungal Pathophysiology in the Gut

- Yeast form, regulated by microbial competition and immune defenses.

- Hyphal transformation.

- Degrade the mucus layer, disrupt epithelial integrity, trigger inflammation.

10. Secretory IgA and Mucosal Defense

- Chronic stress, immune dysfunction, dysbiosis can lower sIgA levels and weaken mucosal immunity.

11. SIFO, SIBO, and Mast Cell Activation

12. Conclusion 

- Root cause approach, multi-factorial

Thanks for tuning in!

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