Increased Intestinal Permeability | Supplements

Intestinal Hyperpermeability

The gastrointestinal tract is a complex and highly specialized system which plays a central role in digestion and nutrient absorption, immune function, and more. When the intestinal barrier is characterized by a state of "hyperpermeability," several biological phenomena may be observed and/or can be linked. Without limitation, these may include alterations in the microbial community or dysbiosis, movement of microorganisms or their components beyond the intestinal epithelial lining, and increased immune activity within the gut environment. Such changes may contribute to a cycle in which the barrier's structure and function remain under ongoing stress, underscoring the central role of intestinal barrier integrity in intestinal health (1).

Intestinal Barrier Anatomy | Key Structures

1. Mucus Layer: The intestinal epithelial lining is coated by a mucus layer whose character shifts along the intestinal length. In the small intestine, this mucus is typically a single, loose layer to allow for effective diffusion and nutrient absorption. By contrast, in the colon there is classically a two-tiered mucus architecture: an inner, denser layer largely impervious to bacterial penetration, and a more loosely organized outer layer inhabited by commensal microorganisms. This mucus matrix is primarily built from gel-forming mucins and water, and it contains biologically active constituents such as secretory immunoglobulin A and antimicrobial peptides, aiding in contributing to mucosal defense (4).
2. Intestinal Epithelium: Beyond this mucus, and moving from the lumen outwards, the intestinal epithelium consists of a monolayer of specialized cells. In expanding upon this notion, the small intestinal epithelium features villi, which are finger-like projections that increase surface area for nutrient absorption; moreover, the spaces or invaginations between villi are termed "crypts" (5, 6).
3. Lamina Propria: Moving outward and past the single layer of epithelial cells, the "lamina propria" contains both blood vessels and lymphatic vessels. Moreover, this connective tissue layer is rich in immune cells, including lymphocytes, macrophages, dendritic cells, mast cells, and more (5, 6).
4. Muscularis Mucosae: Continuing outward, we arrive at the muscularis mucosae, a thin layer of smooth muscle (5, 6).

Tight Junctions

Tight junctions play a crucial role in maintaining the selective permeability of the epithelial barrier, aiding in regulating the paracellular passage (It may be noted that "paracellular" refers to passage which is between epithelial cells.) of ions, water, and other molecules. In more detail, tight junctions are composed of various proteins that aid in "sealing" the spaces between adjacent epithelial cells. The primary transmembrane proteins involved are claudins, occludin, tricellulin, and junctional adhesion molecule (JAM) (7). Likewise, zonula occludens proteins act as scaffolding bridges that link transmembrane tight-junction proteins to the actin cytoskeleton (7).

Tight Junctions & Barrier Disruption

There are several possible factors that can contribute to intestinal barrier disruption. In more detail, inflammatory mediators and microbial components have been shown to alter the organization and regulation of tight junctions within the intestinal epithelium. Evidence indicates that cytokines released during immune activation, along with bacterial products such as lipopolysaccharides (LPS), may impact tight junctions and barrier integrity (7).

Supporting the Intestinal Barrier

Examples of natural compounds, ingredients, or minerals that may aid in supporting intestinal health:

1. Quercetin: A naturally occurring flavonol present in an array of plants including onions and apples. Quercetin may support intestinal health and barrier integrity (8,9).
2. Deglycyrrhizinated Licorice (DGL): Deglycyrrhizinated licorice (DGL) is a form of licorice root extract from which much of the compound glycyrrhizin has been removed. DGL May aid in supporting digestion as well as intestinal health and mucus production (10).
3. Zinc: Zinc is an essential mineral; zinc may aid in supporting intestinal barrier function, tight junction integrity, and more (11, 12, 13).
4. Slippery Elm: Slippery elm contains mucilage polysaccharides and may aid in supporting gastrointestinal health (14).
5. Marshmallow Root: Marshmallow root contains mucilage polysaccharides and may aid in supporting gastrointestinal health (15).
6. Aloe Vera: Aloe vera contains polysaccharides, such as acemannan, and may aid in supporting intestinal barrier function (2, 3, 16).
7. N-Acetylglucosamine (NAG): N-Acetylglucosamine (NAG) is an amino sugar that serves as a building block in the carbohydrate chains of mucins; supplemental NAG may support intestinal barrier integrity (17).
8. Glutamine: Glutamine is an amino acid that serves various functions, including acting as a fuel source for enterocytes (intestinal epithelial cells). Supplemental glutamine can support intestinal barrier integrity (18, 19).

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