In this episode, we go through the gut-immune axis and mycobiome, focusing on the mechanisms underlying intestinal fungal overgrowth. We highlight the roles of the intestinal mucus layer, intestinal epithelial cells, lamina propria, and secretory immunoglobulin A (sIgA) in maintaining homeostasis and defending against fungal overgrowth. We also detail the pathogenic transition of Candida from its commensal yeast form to an invasive hyphal state, as well as the resulting disruptions to immune function.

Topics

1. Introduction to the Gut-Immune Axis and Mycobiome

   - The gut-immune axis and mycobiome.

   - Exploring intestinal fungal overgrowth.

2. Overview of the Gastrointestinal Lining

   - Anatomy of the intestinal lining: lumen and microbiome, mucus layer, epithelial monolayer, and lamina propria.

   - The dual role of the mucus layer: physical and biochemical barrier.

   - Composition of mucus.

3. Goblet Cells and Mucus Production

   - Goblet cells as critical producers of mucin glycoproteins and their role in mucus barrier integrity.

   - Signals for mucin release, such as mechanical stress.

4. The Lamina Propria and Gut-Associated Lymphoid Tissue

   - Layers beneath the epithelium

   - Peyer’s patches, mesenteric lymph nodes, isolated lymphoid follicles, and intraepithelial lymphocytes.

   - Immune tolerance and defense against pathogens.

5. Peyer’s Patches

   - Positioning of Peyer’s patches.

   - The transition of microbial density from the small intestine to the colon and its immune implications.

6. Immune Cells in the Lamina Propria

   - Overview of macrophages, dendritic cells, mast cells, plasma cells, and lymphocytes.

   - Their role in maintaining immunological equilibrium in the gut.

7. The Mycobiome and Pathogenic Transition of Candida

   - Candida’s transition from yeast to hyphal form.

   - Regulation of Candida by microbial competition and immune surveillance.

   - Factors promoting pathogenicity: immune suppression, lacking beneficial microbes, more.

8. Virulence Factors of Candida

   - Secretion of hydrolytic enzymes such as SAPs and phospholipases.

   - Degradation of sIgA and its consequences for immune evasion.

   - Adhesins that facilitate fungal binding.

9. Intestinal Barrier Disruption by Candida

   - Penetration of the mucus layer and epithelial barrier by Candida hyphae.

   - Disruption of tight junctions and the resulting increased intestinal permeability.

   - Inflammatory cascade triggered by fungal antigens and microbial toxins entering the lamina propria.

10. Biofilm Formation

    - The role of biofilms in shielding fungal cells from immune attack and antifungal treatments.

11. Small Intestinal Fungal Overgrowth (SIFO)

    - Intestinal dysmotility, low stomach acid, immunocompromise.

    - Possible symptoms of SIFO.

    - Discussion of the overlap between SIFO, SIBO, histamine intolerance, and other gastrointestinal conditions.

- Root cause.

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