Understanding and Addressing Increased Intestinal Permeability
The gastrointestinal tract is a complex and highly specialized system crucial for nutrient absorption, immune function, and overall health. One critical aspect of gut health is the integrity of the intestinal barrier, which prevents harmful substances from entering the bloodstream. Moreover, this barrier can be compromised, leading to increased intestinal permeability, commonly known as "leaky gut." Understanding the anatomical structure of the gut lining and the factors that contribute to increased intestinal permeability can help identify effective strategies for restoring gut health.
The Structure of the Intestinal Barrier
To appreciate how increased intestinal permeability occurs, we must first understand the layers that make up the intestinal barrier. Starting from the gut lumen and moving outward:
Mucus Layer: The gut is lined with a mucus layer that varies in thickness throughout the intestine. In the small intestine, it forms a thin, discontinuous layer to facilitate nutrient absorption. In contrast, the large intestine has two distinct mucus layers. The inner mucus layer is sterile, devoid of bacteria, and forms a physical barrier to protect the epithelial cells, while the outer layer contains a rich microbiota. Furthermore, this mucus, composed of water, mucins, and glycoproteins, also contains secretory immunoglobulin A and antimicrobial peptides such as trefoil factors, cathelicidins, and ribonucleases that help reinforce the barrier.
Intestinal Epithelium: Beyond the mucus, and moving from the inside of the gut (gut lumen) outwards, we arrive at the intestinal epithelium. The intestinal epithelium is a monolayer of specialized cells renewed every 3-5 days. The epithelium features villi, which are finger-like projections that increase surface area for nutrient absorption, and the spaces between villi, called crypts, house stem cells that replenish the gut epithelial cells, ensuring rapid cell turnover and repair.
Lamina Propria: Moving outward and past the single layer of epithelial cells, we arrive at the lamina propria. This layer contains both blood vessels and lymphatic vessels and is rich in immune cells, including lymphocytes, macrophages, dendritic cells, mast cells, and eosinophils. If an antigen gets past the monolayer of epithelial cells, this army of immune cells is ready to attack and initiate an inflammatory response.
Muscularis Mucosae: Making our way outward again, we arrive at the muscularis mucosae. This thin layer of smooth muscle helps to move and mix the layers above during digestion and peristalsis.
Candida and Intestinal Permeability
Tight junctions are intricate structures that form a barrier between adjacent epithelial cells in various tissues, including the gut. They play a crucial role in maintaining the selective permeability of the epithelial barrier, regulating the passage of ions, water, and other molecules.  To understand how tight junctions function and how they can be disrupted, we need to delve into their molecular makeup and the specific roles of the proteins involved. Here’s a detailed look at the key components and how they function:
Key Components of Tight Junctions
The tight junctions are composed of several key proteins that work together to seal the spaces between adjacent epithelial cells. The primary transmembrane proteins involved are claudins, occludins, and junctional adhesion molecules (JAMs). Claudins are the most critical proteins in tight junctions, with at least 27 different types identified in humans. Occludin is another integral protein that regulates the tight junction’s permeability, particularly influencing the passage of small molecules and ions. Junctional adhesion molecules (JAMs), part of the immunoglobulin superfamily, play a role in cell-cell adhesion, further supporting the tight junction structure.
Interaction with the Cytoskeleton
Inside the cell, the tight junction proteins interact with the cytoskeleton through peripheral membrane proteins, ensuring the structural stability of the junctions. The primary proteins involved in this interaction are the zona occludens proteins (ZO-1, ZO-2, and ZO-3). These ZO proteins act as scaffold proteins, linking the transmembrane proteins (claudins, occludin, and JAMs) to the actin cytoskeleton. This connection is crucial as it provides the necessary support and stability for the tight junctions, allowing them to maintain their barrier function.
Candida's Mechanism of Disruption
When tight junctions are compromised, the gut barrier becomes more permeable, allowing larger molecules, toxins, and pathogens to pass through the epithelial layer and enter the bloodstream. This increased permeability, often referred to as "leaky gut," can lead to a range of health issues. Symptoms of leaky gut include digestive problems (bloating, gas, cramps), food sensitivities, chronic fatigue, skin conditions (eczema, acne), joint pain, and even the development of autoimmune diseases. The body's immune response to these foreign substances can trigger systemic inflammation, exacerbating these symptoms and potentially leading to more severe health conditions.
For example:
Candida is a type of yeast that normally exists in small amounts in the gut microbiota. However, under certain conditions, such as after prolonged antibiotic use or high sugar intake, Candida can overgrow and become pathogenic. This overgrowth can lead to several mechanisms that disrupt the integrity of tight junctions:
Adhesion and Invasion: Candida can adhere to epithelial cells and form biofilms, a structured community of microorganisms encapsulated within a self-produced matrix. These biofilms protect Candida from the host immune response and increase its ability to colonize the gut lining.
Enzyme Secretion: Candida secretes several enzymes, including proteases and phospholipases, which degrade the components of the epithelial cells and tight junctions. Proteases break down proteins like claudins and occludins, while phospholipases disrupt the lipid components of the cell membranes, weakening the tight junctions.
Aldehyde Production: Candida produces acetaldehyde, a toxic metabolite that can cause direct damage to the epithelial cells and the proteins of the tight junctions.
Inflammatory Response: The presence of Candida and its metabolites beyond the lining of epithelial cells can trigger a robust immune response (since we remember that the immune cells of the lamina propria are on the other side of the epithelial cells). This leads to the production of inflammatory cytokines, and these cytokines can modulate the expression and function of tight junction proteins, causing them to become more permeable. As a result, a cycle of inflammation/permeability/microbial escape ensues.
Assuming Candida Overgrowth and Other Potential Pathogens Have Been Addressed, What Can We Do to Support the Integrity of the Gut Lining and Combat Increased Intestinal Permeability?
Key Ingredients to Support Gut Health
Addressing increased intestinal permeability involves repairing the gut lining, reducing inflammation, and restoring the balance of gut microbiota. Several natural ingredients have been shown to support these processes:
Quercetin: A flavonoid that stabilizes mast cells and reduces histamine production, thus decreasing gastrointestinal inflammation.
Bromelain: An enzyme from pineapple that has anti-inflammatory properties and supports digestion. Bromelain can also enhance the absorption of quercetin.
Deglycyrrhizinated Licorice (DGL): Helps soothe and protect the gut lining, reducing inflammation.
Methylsulfonylmethane (MSM): Methylsulfonylmethane (MSM) supports gut integrity by providing bioavailable sulfur essential for synthesizing and repairing tight junction proteins, thus maintaining the epithelial barrier.
Zinc Orotate: An essential mineral that supports the integrity of tight junctions (it has been shown that zinc deprivation results in decreases in expression of claudin-1, occludin, and ZO-1... all of which are critical for maintaining structurally-sound tight junctions).
Marshmallow Root and Slippery Elm: Both provide mucilage, a gel-like substance that coats and soothes the gut lining.
Aloe Vera: Contains polysaccharides that stimulate the secretion of mucus in the gut lining. This increased mucus production helps protect and lubricate the intestinal walls, enhancing the barrier function. Aloe is also anti-inflammatory and antimicrobial as well.
N-Acetyl Glucosamine (NAG): NAG also supports the production of mucin, enhancing the protective mucus layer.
Glutamine: An amino acid that fuels enterocytes, promoting the repair and regeneration of the intestinal lining.
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