Signs of Leaky Gut: Separating Science from Hype

“Leaky gut” is one of the most polarizing terms in health. Functional medicine practitioners call it the root cause of everything from autoimmune disease to depression. Most gastroenterologists, meanwhile, say it’s not a real diagnosis.

The truth is somewhere in the middle. Increased intestinal permeability is a real, measurable phenomenon with solid research behind it. But the way it’s talked about online — and the supplements marketed to “fix” it — often stray far from what the evidence actually supports.

What intestinal permeability actually means

Your intestinal lining is a single layer of epithelial cells connected by tight junction proteins. This barrier has a specific job: absorb nutrients while keeping bacteria, toxins, and undigested food particles out of the bloodstream.

When tight junctions become compromised, the barrier becomes more permeable than it should be. Larger molecules — including bacterial endotoxins (lipopolysaccharides), food antigens, and microbial products — can pass through into the bloodstream.¹

This isn’t a binary switch. Intestinal permeability exists on a spectrum, fluctuates throughout the day, and changes in response to diet, stress, medication, and infection. The question isn’t whether you “have” leaky gut — it’s whether your permeability is elevated enough to drive symptoms.

How it’s measured

Unlike many alternative health claims, intestinal permeability can be objectively measured. The most established method is the lactulose-mannitol test: you drink a solution containing two sugar molecules of different sizes, then measure how much of each appears in your urine.

Mannitol (small) should be absorbed normally. Lactulose (larger) should not pass through an intact barrier. If the lactulose-to-mannitol ratio is elevated, it indicates increased permeability.²

More recent methods include measuring serum zonulin (a protein that regulates tight junction opening) and serum levels of bacterial endotoxins.³

What causes increased permeability

Research has identified several well-documented causes:

Stress

Vanuytsel et al. showed that psychological stress increases intestinal permeability in healthy humans within hours, via a mast cell-dependent mechanism triggered by corticotropin-releasing hormone.⁴

NSAIDs

Non-steroidal anti-inflammatory drugs (ibuprofen, aspirin, naproxen) are one of the most common causes. Bjarnason et al. demonstrated that NSAIDs increase intestinal permeability within 24 hours of ingestion, and chronic use causes persistent barrier damage.⁵

Alcohol

Bode and Bode reviewed decades of evidence showing that both acute and chronic alcohol consumption disrupts tight junction proteins, increases endotoxin translocation, and promotes gut inflammation.⁶

Gut infections and dysbiosis

Bacterial, viral, and parasitic infections can directly damage the intestinal barrier. Even after the infection resolves, permeability can remain elevated for weeks or months.⁷

Diet

Processed food, emulsifiers, and high-sugar diets have been associated with increased permeability in both animal and human studies. Chassaing et al. showed that common food emulsifiers (polysorbate 80 and carboxymethylcellulose) disrupted the gut barrier and promoted inflammation in animal models.⁸

Signs that may indicate increased permeability

Based on the research, the following symptoms and conditions have been associated with elevated intestinal permeability:

Digestive symptoms

Chronic bloating, gas, diarrhea, constipation, and abdominal pain are the most direct signs. Dunlop et al. found that post-infectious IBS patients had measurably increased intestinal permeability compared to those who recovered without developing IBS.⁹

Food sensitivities

When the gut barrier is compromised, food antigens that normally wouldn’t reach the immune system can trigger reactions. This may explain why food sensitivities often develop suddenly in adulthood — the foods haven’t changed, but the barrier has.¹

Fatigue and brain fog

Bacterial endotoxins that cross a leaky barrier trigger inflammatory cytokines (IL-6, TNF-alpha) that affect brain function. Dantzer et al. documented how peripheral inflammation produces fatigue, cognitive impairment, and low mood — collectively called “sickness behavior.”¹⁰

Skin issues

The gut-skin axis is well-established. Increased intestinal permeability has been documented in patients with eczema, psoriasis, and acne. Humbert et al. found elevated intestinal permeability in patients with chronic skin conditions compared to healthy controls.¹¹

Joint pain

Increased intestinal permeability has been found in patients with rheumatoid arthritis, ankylosing spondylitis, and other inflammatory joint conditions. The proposed mechanism involves bacterial products crossing the gut barrier and triggering systemic inflammatory responses.¹²

What the research says about “fixing” it

This is where things get complicated. The supplement industry sells dozens of “leaky gut repair” products — L-glutamine, collagen, zinc carnosine, slippery elm, bone broth. Some have preliminary evidence; most don’t have the clinical trials to support the claims.

What has evidence

Removing the cause. The most consistently effective intervention is identifying and removing whatever is damaging the barrier. If it’s NSAIDs, stopping them allows the barrier to heal. If it’s stress, stress management helps. If it’s a specific food trigger, eliminating it reduces the inflammatory load.⁵

Dietary changes. A diet rich in fiber, polyphenols, and fermented foods supports barrier function through increased short-chain fatty acid production (especially butyrate), which directly nourishes intestinal epithelial cells. Desai et al. showed that fiber-deprived diets cause gut bacteria to consume the protective mucus layer instead, compromising barrier integrity.¹³

Zinc. Zinc supplementation has evidence for improving intestinal barrier function, particularly in cases of zinc deficiency or acute diarrheal illness. Sturniolo et al. demonstrated that zinc supplementation reduced intestinal permeability in Crohn’s disease patients.¹⁴

What lacks strong evidence

L-glutamine is widely promoted but clinical trial results are mixed. Bone broth and collagen supplements have essentially no controlled human trials for intestinal permeability despite widespread marketing. Slippery elm and other botanical supplements have traditional use but minimal clinical validation.

The food sensitivity connection

Here’s why intestinal permeability matters for anyone trying to identify food triggers: if your barrier is compromised, you’re more likely to react to foods that aren’t inherently problematic.

This is important because it means some food “sensitivities” are actually barrier problems. Fix the barrier, and the sensitivities may resolve. This is one reason elimination diets sometimes seem to “cure” multiple sensitivities at once — the elimination period gives the gut a chance to heal, not just avoid triggers.

It also means that identifying food triggers without addressing the underlying barrier issue may lead to an ever-expanding list of problematic foods. The real solution often involves both finding your specific triggers and supporting barrier repair through diet, stress management, and removing other damaging factors.

The bottom line

• Increased intestinal permeability is real and measurable, not a made-up diagnosis
• Stress, NSAIDs, alcohol, infections, and processed food are the most well-documented causes
• Digestive symptoms, food sensitivities, fatigue, skin issues, and joint pain are associated with elevated permeability
• Removing the cause (stress, medications, dietary triggers) is the most evidence-supported intervention
• A fiber-rich, whole foods diet supports barrier repair through butyrate production
• Many supplements marketed for leaky gut lack sufficient clinical evidence
• Food sensitivities and barrier dysfunction often coexist — addressing both produces better outcomes than targeting either alone

If you suspect your gut barrier is compromised, the most practical first step is an elimination protocol that simultaneously removes potential triggers and supports gut healing through whole foods — rather than spending money on unvalidated blood tests or supplement stacks.

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