Intestinal Permeability: Most Effective Dietary Supplements

The intestinal barrier is essential for human health; it allows nutrient absorption while preventing harmful substances from entering the body. This barrier, covering approximately 400 m², consumes nearly 40% of the body's energy expenditure. It is composed of an external physical barrier and an internal immunological barrier. A serious failure of this barrier can lead to systemic inflammation, increasing intestinal permeability and possibly resulting in multi-organ failure. Increased intestinal permeability has been observed in various diseases such as Parkinson's disease, obesity, and type 2 diabetes.

Role of Intestinal Permeability in Diseases

New data suggest that the intestinal barrier and gut microbiota play a role in many diseases. Indeed, increased intestinal permeability has been observed in several different conditions, such as Parkinson's disease, obesity, and type 2 diabetes. For instance, in inflammatory bowel diseases (IBD), proteins that keep intestinal cells tightly linked are altered, allowing bacteria to cross the intestinal wall more easily, which is manifested by an increase in the urinary secretion of specific markers. Similarly, in irritable bowel syndrome (IBS), a similar alteration of tight junction proteins is observed, increasing both paracellular and transcellular permeability, with bacteria crossing the intestinal wall more easily. In celiac disease, the structure of tight junction proteins is modified, leading to increased absorption of gliadin, a wheat protein, and an increase in levels of zonulin, a protein that regulates intestinal permeability. Obesity is also linked to increased intestinal permeability, with dietary lipids inducing this increase and high levels of zonulin and lipopolysaccharide in the blood. Type 2 diabetes also shows an increase in intestinal permeability, with elevated levels of lipopolysaccharide and zonulin in the blood, indicating an impaired intestinal barrier. Similar patterns are observed in neurodegenerative diseases such as Alzheimer's and Parkinson's, where increased bacterial absorption and raised permeability markers in the blood are detected. Finally, in major depressive disorder, intestinal permeability markers such as I-FABP (Intestinal Fatty Acid Binding Protein) and zonulin are elevated in the blood.

Intestinal Barrier and Regulation

The intestinal barrier is composed of epithelial cells linked by tight junctions, regulating the passage of molecules. Tight junctions include proteins like claudins and occludin, which form complexes linking the cells together. In addition to this physical barrier, chemical substances, digestive secretions, and the gut microbiota also contribute to maintaining barrier function. The homeostasis of the intestinal barrier depends on the relationship between the gut microbiota and the epithelium. Factors like diet, infections, toxins, and lifestyle can influence intestinal permeability. An imbalance in this relationship can have negative health consequences.

Nutritional Treatment Protocol

Human and animal studies have shown that supplementation with antioxidant nutrients and extracts prevents oxidative damage and helps restore normal mucosal barrier function. 2 Quercetin is a natural flavonoid with antioxidant, anti-inflammatory, and anticancer properties. It has been shown to improve intestinal barrier functions. Mast cells play an important role in the pathogenesis of mucosal inflammation and increased intestinal permeability. Quercetin helps control intestinal inflammation by inhibiting the release of histamine by human intestinal mast cells. It has also been shown to inhibit gene expression and production of pro-inflammatory cytokines. 2 Ginkgo biloba extract has antioxidant and free radical-trapping properties with cytoprotective effects on gastrointestinal mucosal cells. Oral supplementation with Ginkgo biloba extract has been shown to reduce macroscopic and histological damage to the colonic mucosa in vivo and significantly decrease pro-inflammatory cytokines in experimentally induced ulcerative colitis. It has also been shown that ginkgo prevents the increase in intestinal permeability and associated mucosal damage from small intestinal ischemia in a dose-dependent manner in animal models. 2 Vitamins C and E play an essential role in protecting intestinal mucosal cells from oxidative damage and free radicals. In a clinical trial, oral supplementation with 300 mg of vitamin E reduced inflammation in the colonic mucosa of patients with ulcerative colitis. Another study conducted in IBD patients showed a significant decrease in vitamin C levels in mucosal tissues compared to non-IBD controls. 2 Zinc appears to play an essential role in maintaining normal intestinal permeability and controlling inflammation. Zinc deficiency has been shown to disrupt mucosal barrier function and increase the secretion of inflammatory mediators in human intestinal epithelial cells. Moreover, zinc has cytoprotective activity in the gastrointestinal tract and helps stabilize intestinal mast cells. 2 Probiotics help maintain or restore beneficial gut microflora and prevent or treat gastrointestinal disorders and associated systemic conditions. Probiotic supplementation can be beneficial in the treatment or prevention of IBD, irritable bowel syndrome, food allergy, atopic dermatitis, eczema, infectious diarrhea, antibiotic-associated diarrhea, chemotherapy-induced intestinal damage, and other human diseases. 2 L-glutamine is an important energy source for intestinal mucosal cells and is essential for the normal structure and function of mucosal membranes. Glutamine appears to be needed for the normal production of secretory immunoglobulin A (IgA) in the intestines. Secretory IgA are the most abundant immunoglobulins in external secretions and play a key role in the normal function of the intestinal mucosa as an immune barrier. 2 N-acetyl-D-glucosamine (NAG) is a natural amino glycan present in high concentrations in the intestinal mucus, secretory IgA, and other immunoglobulins. Intestinal mucus plays a crucial role in host protection by providing a mechanical and immunological barrier against toxins, antigens, and bacteria in the intestinal lumen. 2 Phosphatidylcholine is a constituent of human bile and a key component of the hydrophobic mucus that protects the gastrointestinal mucosa. Studies have shown that oral intake of PC can prevent intestinal lesions and reduce permeability to intestinal endotoxins. 2 Polyunsaturated fatty acids support the integrity of the epithelial barrier and normal mucosal permeability. Indeed, it has been shown that gamma-linolenic acid (GLA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) are incorporated into the phospholipid fraction of human mucosal epithelial cell membranes and reduce mucosal permeability defects caused by inflammatory cytokines. 2 Digestive enzymes: Adequate digestion is a necessary condition for normal gastrointestinal function and overall health. Deficiencies in digestive enzymes and imbalances in gastrointestinal pH can result in impaired digestion, contributing to nutrient malabsorption, food intolerance, food allergy, autoimmune diseases, bacterial overgrowth, and gastrointestinal discomfort symptoms. Insufficient pancreatic enzyme activity can also lead to increased intestinal permeability. 2 Dietary fibers: Dietary fibers play an important role in maintaining normal gastrointestinal function and health. Studies indicate that fibers help maintain the normal barrier function of the intestinal mucosa. Soluble fibers are fermented by colonic microflora, promoting the growth of beneficial bifidobacteria. The fermentation of dietary fibers by colonic microflora is the primary source of short-chain intestinal fatty acids, including butyric acid, which is a significant energy source for intestinal epithelial cells and plays a key role in colonic homeostasis. Butyrate has been shown to inhibit inflammation, reduce oxidative stress, and maintain normal colonic mucosa barrier function.