A claim you hear on longevity podcasts

Does gluten cause leaky gut in everyone?

The claim checked: Gluten causes some leaky gut in nearly everyone who eats wheat Hear it at 21:56

What do the studies say?

Mixed

Three of six studies disagree. In 46 healthy adults, changing the gluten dose did not change a standard test of how leaky the gut is. In people sensitive to gluten without celiac disease, permeability was not higher, and in one study it was lower than in the comparison group. One trial found that gluten changed the gut barrier in patients with diarrhea-type irritable bowel syndrome.

Computed from 6 studies that test this point, each judged by two readers, in full. 5 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“Alessio Fasano at Harvard has done the work on this. Everybody, pretty much everybody who eats wheat, it causes some level of leaky gut. It causes some disruption in the intestinal barrier.”
Mark Hyman, The Doctor's Farmacy · If I Could Only Do ONE Thing to Treat Chronic Disease, This Would Be It · 21:56 on YouTube
Episode check Modern wheat has much more gluten, the episode says. Seven of eight studies disagree. 5 claims checked against 36 studies · 10 chapters not checked yet See the whole episode →
The point checked Mixed

Gluten (gliadin) increases intestinal permeability in people without celiac disease

Agree 1

controlled trial · 2013 · landmark

“Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8–positive patients.”

A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology
Who: Mayo Clinic patients with diarrhea-predominant IBS (43 female, 2 male), celiac disease excluded by serology or biopsy, not selected for prior gluten response; 22 HLA-DQ2/8 positive
PMID 23357715

Partly agree 2

other primary study · 2017

“Nevertheless, a high degree of interindividual variability prevented this from achieving statistical significance (p=0.07).”

Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression. Lab Invest
Who: Non-celiac patients with diarrhea-predominant IBS (celiac excluded by biopsy or serology), from a prior Mayo Clinic gluten-free vs gluten-containing diet trial
PMID 27869798

other primary study · 2016

“It is important to emphasise that this study does not address the potential mechanism or molecular trigger(s) responsible for driving the presumed loss of epithelial barrier integrity and microbial translocation.”

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut
Who: 80 adults with non-coeliac wheat sensitivity, 40 with active coeliac disease and 40 healthy controls (Bologna, Italy); 20 NCWS before and after a wheat-free diet
PMID 27459152

Disagree 3

trial or observed group · 2011 · landmark

“Interestingly, the LA/MA ratio in GS patients was also significantly reduced relative to DC ( P = 0.0308) (Figure 1 ).”

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med
Who: 26 gluten-sensitive (non-celiac) patients, 42 active celiac patients and 39 dyspeptic controls in Naples; permeability tested in 13 GS, 11 CD and 14 controls
PMID 21392369

controlled trial · 2025

“Hypothesised potential mediators of these effects (intestinal permeability, hsCRP and CAR) did not differ between nutrients or groups.”

Impact of Acute and Sub-Acute Gluten Exposure on Gastrointestinal Symptoms and Psychological Responses in Non-Coeliac Gluten Sensitivity: A Randomised Crossover Study. United European Gastroenterol J
Who: Adults with non-coeliac gluten sensitivity (coeliac excluded by serology, HLA testing and biopsy when indicated) and healthy controls, on a gluten-free diet during the study
PMID 40138597

other primary study · 2026

“Importantly, variations in the gluten dose did not affect the LMR, indicating that overall intestinal permeability was not substantially affected by gluten intake in healthy individuals.”

Standardizing Intestinal Permeability Assessment: Optimization of Gluten Dose and Urine Collection Times for u-GIP and Lactulose:Mannitol Ratio in Healthy Volunteers. Int J Mol Sci
Who: 46 healthy adult volunteers across four protocols (Spain)
PMID 41828523

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