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How do environmental factors contribute to "leaky gut" syndrome?

Both external and internal conditions can result in the development of a “leaky gut”. Guidance from stool test results can help clinicians choose appropriate interventions to restore gut homeostasis and barrier functions.

Gut homeostasis and immunity occur through a complex interplay of innate and adaptive immune responses. The gut mucosa is the largest and most dynamic immunological environment of the body. It's often the first point of pathogen exposure and many microbes use it as a doorway into the rest of the body. The gut immune system therefore needs to be ready to respond to pathogens but, at the same time, is constantly exposed to innocuous environmental antigens, food particles and beneficial/commensal microflora which need to be tolerated. The term “leaky gut” has moved into common usage to describe altered intestinal permeability. While neither the term “leaky gut” nor the mechanisms that cause the problem are fully understood at present, intestinal permeability is an active area of research.

The gut mucosa is the innermost layer of the gastrointestinal tract; the mucosa lines the gut lumen, and provides an exchange interface for nutrient absorption. Gut cells (enterocytes) cooperate with cells of the intestinal immune system; they help maintain a tolerant state toward dietary and gut microbiome antigens. Tight junctions between the mucosal enterocytes are primary factor for gut barrier integrity. Immune exclusion, the prevention of antigen entry into systemic circulation, requires both a healthy gut barrier and adequate levels of secretory IgA (sIgA). A variety of important regulatory cytokines (signal molecules) are known to be secreted by enterocytes in response to stimulation by stress hormones, ingested food, pathogens, environmental toxins, minerals or vitamins.

Leaky Gut Illistration

When the gut mucosa is irritated, injured, or inflamed, the mucosal enterocytes release “alarm molecules” which reduce the expression of tolerance signals and promote the release of pro-inflammatory signals that disrupt the gut barrier. Barrier disruptions increase gut “leakiness” and attract white blood cells to perpetuate local inflammation that damages the gut mucosal barrier and underlying tissues. A pro-inflammatory gut environment inflames the gut mucosa and decreases the effectiveness of the mucosal barrier. If the disruption is short-lived, the inflammation may dissipate, and homeostasis may be restored. If the disruptions continue, then the pro-inflammatory patterns may become chronic and dominate the intestinal terrain, barrier function is lost or altered, and food allergies or food intolerances may develop as the mucosal barrier loses integrity.

Fortunately, clinicians have functional stool testing to evaluate a patient’s “leaky gut” potential, as well as clinical tools to help improve intestinal permeability. Like every other health problem, the development of a leaky gut is always a combination of internal and external factors. Many of these factors will be explored in future blogs.

  • Internal factors may include:
    • Comorbid inflammation
      • Allergy/sensitivity
      • Inflammatory bowel disorders
        • Celiac, IBD, IBS
      • Mitochondrial function
    • Genetics
    • Nutritional status
    • Psychological status (stress)
  • External factors may include:
    • Diet
      • Highly processed, high-carb/high-fat
      • Poor fruit/vegetable intake
    • Environmental exposure
      • Food allergy, food sensitivity
      • Non-Celiac gluten sensitivity (HLA-DQ2/8-positive)
    • Microbiome status
      • Pathogens, parasites
      • Loss of microbiome diversity or dysbiosis
    • Nutritional status
      • Vitamin or mineral deficiency

Stool tests, such as US BioTek’s GI Advanced Profile, can provide guidance on many of the likely causes of leaky gut, and serial testing can demonstrate improvements as therapeutic interventions restore homeostasis.

GI - Advanced Profile Sample Report

PCR microbiome mapping can detect pathogens, parasites and gut microbiome bacteria, while stool chemistries provide valuable information about gastrointestinal function and immune status:

  • Occult blood indicates bleeding in the gastrointestinal tract
  • Short-chain fatty acids are essential anti-inflammatory signal molecules; low levels may exacerbate inflammation
  • Calprotectin and fecal Zonulin elevate when mucosal inflammation is present
  • Elastase is a biomarker for protein digestion and exocrine pancreatic function; low levels indicate problems with digestion/assimilation of nutrients
  • Steatocrit (fecal fat stain) indicates the efficiency of fat assimilation
  • Secretory IgA is an important “first-line” defense for the gut mucosal barrier; low levels may increase risk of infection, food allergy/sensitivity
  • b-glucuronidase elevations can increase the recirculation of toxic liver phase I metabolites in circulation
  • Anti-gliadin IgA indicates the presence or absence of wheat/gluten in the diet; many patients need to avoid these inflammatory foods

GI Test Results After Intervention

Once stool testing identifies causative factors then therapeutic interventions can be applied to restore homeostasis. A second stool test 3-4 months later can be used to ensure that the patient’s gut is responding to the interventions as intended. Based upon test results, interventions to strengthen the gut mucosal barrier and improve function may include:

  • Identify and eliminate food allergies and sensitivities
  • Identify and eliminate mold contamination common in processed foods, grains, and dried foods. Ingested mycotoxins can disrupt mucosal barrier functions and the microbiome.
  • Amino acid supports:
    • Glutamine
    • Taurine
    • Tryptophan
    • Bioactive whey proteins (immunoglobulins, etc.)
  • Fat intake – eliminate saturated fats, consider a lower-fat diet and emphasize polyunsaturated omega-3 fats
  • Flavonoids:
    • Quercetin, myricetin, and kaempferol
  • Read labels and avoid inflammatory foods and foods known to increase permeability:
    • Gliadin, a protein found in the gluten-containing grains wheat, rye and barley
    • Carrageenan, derived from seaweeds, is widely used in foods and pharmaceuticals
    • Chitosan, derived from crab or shrimp shells and is widely used in processed foods
  • Minerals such as calcium and zinc are essential for normal barrier function.
  • Normalize intestinal motility
    • Correct digestive disorders, initiate stress management, evaluate and eliminate food allergens, sensitivities, mycotoxins, chemicals, etc.
  • Phenolic compounds [such as tannins, epigallocatechin gallate (EGCG), chlorogenic acid (coffee), gymnemic acid (stevia)] to inhibit intestinal glucose transporters.
  • Probiotics can increase the production of beneficial short chain fatty acids and also synthesize B vitamins and vitamin K. Support microbiome diversity with plant fiber.
  • Vitamins A and D support tolerant, anti-inflammatory immune responses. 

Accumulating evidence indicates that gut health = human health. Guided by comprehensive tests, such as US BioTek’s GI Advanced Profile, clinicians can identify and correct many contributing causes of leaky gut.



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X-ray of stomach and GI tract

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