Leaky Gut Explained: What It Is What Causes It and How to Heal It

May 24, 2026

Leaky Gut Explained: What It Is, What Causes It, and How to Heal It

By Dr. Onikepe Adegbola, MD PhD — Johns Hopkins-trained physician-scientist and founder of Casa de Sante

Key Takeaways

"Leaky gut" is the layperson's term for increased intestinal permeability — a real, measurable phenomenon documented in thousands of peer-reviewed studies. The debate isn't whether it exists, but whether it's a cause or consequence of disease (evidence supports both).
The intestinal barrier is a single layer of cells joined by tight junction proteins. When these junctions loosen, molecules that should stay in the gut (bacterial toxins, food proteins, inflammatory mediators) enter the bloodstream.
This triggers a systemic immune response: the body attacks these foreign molecules, producing chronic inflammation that can manifest as joint pain, brain fog, skin issues, fatigue, autoimmune flares, and worsened IBS.

What Causes Intestinal Permeability

Dietary Factors

Alcohol: Directly damages the intestinal epithelium and disrupts tight junction proteins. Even moderate alcohol increases permeability within hours.
Processed food additives: Emulsifiers (polysorbate 80, carboxymethylcellulose) thin the mucus layer and increase permeability in animal studies. Found in ice cream, salad dressings, sauces, and processed foods.
Excess sugar and refined carbs: Feed pathogenic bacteria that produce toxins damaging to the gut lining.
Gluten: Triggers zonulin release in susceptible individuals. Zonulin opens tight junctions. This occurs in celiac disease and, to a lesser extent, in some non-celiac individuals.

Medications

NSAIDs (ibuprofen, aspirin): Directly increase intestinal permeability by inhibiting prostaglandin synthesis in the gut lining. Even a single dose can measurably increase permeability.
PPIs (proton pump inhibitors): Alter gut pH → microbiome changes → increased permeability. Also associated with SIBO.
Antibiotics: Destroy beneficial bacteria that maintain the gut barrier. Recovery can take months.

Lifestyle Factors

Chronic stress: Cortisol directly increases tight junction permeability. Stress is arguably the most underrecognized cause of leaky gut.
Sleep deprivation: Even partial sleep restriction increases intestinal permeability markers.
Excessive exercise: Intense endurance exercise (marathon running) causes temporary intestinal permeability. "Runner's gut" is a real phenomenon.

Gut-Specific Causes

Dysbiosis: Loss of beneficial bacteria (especially Akkermansia muciniphila) that maintain the mucus layer.
SIBO: Bacterial overgrowth in the small intestine damages the epithelial lining.
Food intolerances: Ongoing exposure to trigger foods causes localized inflammation that compromises the barrier.
Infections: Gastroenteritis, parasites, Candida overgrowth can damage the epithelium.

Testing for Intestinal Permeability

Lactulose-mannitol test: The gold standard. Drink a solution of lactulose (large molecule, shouldn't cross intact barrier) and mannitol (small molecule, crosses easily). Urine is collected and tested. High lactulose/mannitol ratio = increased permeability.
Zonulin (blood test): Zonulin is the protein that opens tight junctions. Elevated serum zonulin correlates with intestinal permeability. Available through functional medicine providers.
Calprotectin (stool test): Marker of intestinal inflammation. Not specific to permeability but correlates.

Healing Protocol

Step 1: Remove

Remove dietary triggers (identified through elimination diet or testing)
Minimize NSAIDs (use acetaminophen when possible)
Reduce alcohol (ideally eliminate during healing)
Address SIBO if present
Minimize processed food additives

Step 2: Replace

Digestive enzymes to ensure complete digestion (undigested food particles irritate the gut lining)
Adequate stomach acid (some patients benefit from betaine HCl with meals)

Step 3: Repair

Glutamine: The primary fuel for intestinal epithelial cells. 5-10g daily. Most studied gut repair nutrient.
Collagen/glycine: Provides the amino acids for tight junction protein synthesis.
Zinc: Required for tight junction integrity. Zinc carnosine specifically studied for gut barrier repair.
Vitamin A: Supports mucosal immunity and epithelial cell turnover.
Omega-3 fatty acids: Anti-inflammatory, support resolution of gut inflammation.

Step 4: Reinoculate

Probiotics: Lactobacillus and Bifidobacterium strains support barrier function.
Prebiotics: Feed beneficial bacteria that produce butyrate (the primary fuel for colonocytes and a tight junction supporter).
Fermented foods (if tolerated): Natural source of diverse beneficial bacteria.

Step 5: Rebalance

Stress management (cortisol is a direct cause of permeability)
Sleep optimization (repair happens during sleep)
Regular moderate exercise (improves gut blood flow and microbiome diversity)

🛒 Gut Barrier Repair Kit

Collagen Peptides — Provides glycine, proline, and glutamine — the three amino acids most critical for gut barrier repair. Collagen peptides specifically support tight junction protein synthesis and mucus layer restoration. This is the cornerstone of any gut repair protocol. Take 10-15g daily for 8-12 weeks for measurable barrier improvement.
FODMAP Enzymes + Probiotics — Addresses Steps 2 and 4 simultaneously: enzymes ensure complete digestion (preventing undigested food from irritating the barrier) while probiotics reinoculate with barrier-supporting strains. Postbiotics provide immediate butyrate — the fuel that colonocytes need for repair.
Daily Vitamin — Zinc for tight junction integrity, vitamin A for mucosal immunity, vitamin D for immune regulation, and all the cofactors needed for the enzymatic processes of barrier repair. Micronutrient deficiencies slow healing — the vitamin removes this bottleneck.

Medical Disclaimer: This article is for educational purposes only. While intestinal permeability is a documented phenomenon, many "leaky gut" claims in wellness media are exaggerated or unsupported. Work with a qualified healthcare provider for diagnosis and treatment. Rule out celiac disease, IBD, and other conditions before attributing symptoms to permeability alone. Dr. Adegbola is the founder of Casa de Sante.

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