The human gut, a vast and complex ecosystem, plays a pivotal role in our overall health. Dysfunction of the gut barrier, often referred to as "leaky gut" or increased intestinal permeability, has been increasingly linked to a range of gastrointestinal (GI) and non-GI diseases. The gut barrier is the body's most important defense system. The surface of the intestinal tract is approximately 7000-8000m2, the largest interface between the human body and the external environment. This article delves into the intricate relationship between dietary factors, intestinal permeability dysfunction, and related diseases, offering insights into how targeted dietary interventions can promote gut health and potentially contribute to weight loss.
Understanding the Gut Barrier and Its Function
The gut barrier is a complex system designed to selectively allow the absorption of nutrients while preventing harmful substances from entering the bloodstream. It includes the mucus layer, commensal microbiota, and a single layer of intestinal epithelium. The 20‐μm‐thick layer of intestinal epithelium contains enterocytes, endocrine cells, microfold (M) cells, goblet cells, and Paneth cells in the small intestine. There are more goblet cells and no Paneth cells in the colon.
Components of the Gut Barrier
Mucus Layer: This layer, composed of water and glycosylated proteins, acts as a physical barrier, preventing direct contact between microbiota, large molecules, and epithelial cells. In the colon, the mucus layer is further divided into an inner and outer layer.
Commensal Microbiota: The gut microbiota provides nutrient metabolism, participates in growth and immune regulation, eliminates pathogenic microorganisms, and maintains gut barrier integrity and normal homeostasis. This diverse community of microorganisms aids in nutrient metabolism, immune regulation, and the elimination of pathogens. A balanced gut microbiota is crucial for maintaining gut barrier integrity.
Intestinal Epithelium: This single layer of cells, including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, forms a selective barrier. Enterocytes, the most abundant type of epithelial cell, absorb nutrients and secrete hormones. Goblet cells secrete mucus, while Paneth cells produce antimicrobial peptides (AMPs) that play a role in host immunity. M cells are in the epithelium covering mucosa‐associated lymphoid tissues, such as the Peyer's patches of small intestine. M cells actively transport luminal antigens to underlying lymphoid follicles to initiate an immune response.
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Tight Junctions and Adherens Junctions
Epithelial cells are connected by tight junctions (TJs) and adherens junctions (AJs), protein complexes that regulate the passage of ions, solutes, and microbes across the gut barrier. TJ connects in the apex of adjacent cells to regulate ion, solute, and microbe diffusion across the gut barrier and maintain homeostasis. AJ is more basal than TJ. TJs, located at the apex of adjacent cells, control the diffusion of substances across the gut barrier, while AJs provide strong adhesion between cells. Impaired integrity of intestinal barrier and structure of the TJ barrier may trigger local or systemic inflammation and diseases. It results in increasing intestinal permeability which allows antigens, endotoxins, pathogens, and other proinflammatory substances to pass through intestinal barrier into circulation.
The Gut-Associated Lymphoid Tissue (GALT)
Beneath the epithelial layer lies the GALT, a network of immune cells that includes dendritic cells (DCs), macrophages, T cells, and B cells. These cells work together to maintain immune homeostasis and respond to threats. Plasma cells release secretory immunoglobulin A (slgA).
Dietary Factors and Gut Health
Food is not only a source of nutrition but also a key modulator of gut microbiota composition and function. Diet can alter the intestinal barrier and impact gut homeostasis. Certain foods and dietary supplements can promote gut health, while others may disrupt gut function.
Foods and Supplements That Promote Gut Health
Fiber-Rich Foods: Dietary fiber, found in fruits, vegetables, and whole grains, promotes the growth of beneficial bacteria and the production of short-chain fatty acids (SCFAs), which nourish the gut lining. Physical exercises regulate gut microbiota diversity; increase abundance of short‐chain fatty acids (SCFAs); and provide long‐term benefits to the gut barrier.
Probiotics: These live microorganisms, found in fermented foods like yogurt and kefir, can help restore balance to the gut microbiota.
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Prebiotics: Non-digestible food components, such as inulin and fructooligosaccharides, serve as food for beneficial bacteria, promoting their growth and activity.
Glutamine: This amino acid is an important energy source for intestinal cells and can help maintain gut barrier integrity.
Zinc: An essential mineral, zinc supports gut barrier function and helps regulate inflammation.
Foods and Medications That May Alter Gut Function
High-Sugar and High-Fat Diets: These diets can promote the growth of harmful bacteria and increase intestinal permeability.
Processed Foods: Additives and emulsifiers in processed foods can disrupt the gut microbiota and impair gut barrier function.
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Alcohol: Excessive alcohol consumption can damage the gut lining and increase intestinal permeability.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): These medications can irritate the gut lining and increase intestinal permeability.
Antibiotics: While antibiotics can be life-saving, they can also disrupt the gut microbiota, leading to dysbiosis and increased intestinal permeability.
Leaky Gut and Related Diseases
Increased intestinal permeability, or "leaky gut," occurs when the gut barrier becomes compromised, allowing harmful substances to enter the bloodstream. This can trigger local or systemic inflammation, contributing to a variety of diseases.
Mechanisms of Leaky Gut-Related Diseases
Inflammation: The passage of antigens, endotoxins, and pathogens across the compromised gut barrier triggers an immune response, leading to chronic inflammation.
Autoimmunity: Leaky gut has been implicated in autoimmune diseases, where the immune system mistakenly attacks the body's own tissues.
Metabolic Disorders: Increased intestinal permeability can contribute to insulin resistance, obesity, and other metabolic disorders.
Gastrointestinal Disorders: Leaky gut is associated with conditions such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease.
Unexpected or prolonged psychological and physiological stress threatens intestinal barrier homoeostasis which responds through gut-brain axis, hypothalamic-pituitary-adrenal axis and sympathetic nerve system (SNS), leading to autoimmune and other disorders.
Dietary Influences on Leaky Gut-Related Diseases
Gluten: In individuals with celiac disease, gluten triggers an immune response that damages the gut lining, leading to increased intestinal permeability.
Dairy: Some individuals may experience increased intestinal permeability in response to dairy products, particularly casein.
Food Additives: Emulsifiers, artificial sweeteners, and other food additives can disrupt the gut microbiota and impair gut barrier function.
Dietary Strategies for Weight Loss and Gut Health
While more research is needed, some evidence suggests that dietary strategies that promote gut health may also contribute to weight loss.
The Gut Microbiota and Weight Management
SCFA Production: SCFAs, produced by beneficial bacteria, can influence energy metabolism and appetite regulation.
Inflammation: Chronic inflammation, often associated with obesity, can be modulated by dietary interventions that promote gut health.
Gut Hormone Regulation: The gut microbiota can influence the production of gut hormones that regulate appetite and satiety.
Practical Dietary Recommendations
Prioritize Whole, Unprocessed Foods: Focus on a diet rich in fruits, vegetables, whole grains, and lean protein sources.
Limit Sugar and Processed Foods: Reduce intake of sugary beverages, processed snacks, and foods high in unhealthy fats.
Incorporate Fermented Foods: Include fermented foods like yogurt, kefir, and sauerkraut in your diet to support a healthy gut microbiota.
Consider Probiotic and Prebiotic Supplements: These supplements may be beneficial for individuals with gut dysbiosis or those seeking to improve their gut health.
Manage Stress: Practice stress-reducing techniques such as yoga, meditation, or spending time in nature, as stress can negatively impact gut health.
Measuring Intestinal Permeability
Many measurement tools exist to measure intestinal permeability ex vivo and in vitro, such as Ussing chamber, assessing urinary excretion probes, like the lactulose:mannitol ratio (LAMA), sucralose, sucrose, PEG4000/400, and 51Cr‐EDTA; bacterial‐related tests, like assays of serum lipopolysaccharides (LPSs) and other bacteria toxins, using IgA/IgM responses to Gram‐negative bacteria, plasma D‐lactate, fecal Butyrate production, fecal Hemolysin test; tests for biomarkers like plasma citrulline, plasm FABP, plasma and urine α‐glutathione S‐transferase (αGST), serum zonulin enzyme-linked immunosorbent assay (ELISA), urine claudin‐3, fecal calprotectin, and α1‐anti‐trypsin test; histological approaches like Western blot for TJ expression, Goblet cell analysis, and shedding of epithelium; others like serum fluorescein isothiocyanate dextran (FITC‐d; Vuong et al., 2021), and endomysial (EMA) and tissue transglutaminase (TTG) antibodies specifically for celiac disease, and so on. Human gut biopsies, confocal endomicroscopy, and endoscopic mucosal impedance also are used for assessing intestinal permeability.