Causes of Leaky Gut
1) Poor Diet
Unhealthy diets can create an imbalance in the intestinal barrier. These diets include:
- Low-fiber diets [R].
- Diets high in saturated fats [R].
- Diets high in fats and sugars (a typical western diet) [R].
- Processed food containing emulsifiers [R].
For example, pregnant women who ate more healthily (more omega-3 fatty acids, fiber, vitamins, and minerals) had a lower intestinal permeability (measured by zonulin) [R].
A high-fat diet increases gut permeability by reducing tight junction protein production in mice [R].
2) Lectins
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586524/
Lectins are proteins that are especially concentrated in seeds (grains, legumes, nuts) and tubers (potatoes).
Lectins can be beneficial by stimulating the immune system. However, they can also bind to the surface of gut-lining cells and disturb the gut barrier [R].
When lectins cause leaky gut, both dietary and bacterial antigens (inflammatory agents) leak into the blood and activate the immune system [R, R, R, R].
Some dietary sources of lectins, such as wheat, can directly open tight junctions in gut cells (by increasing zonulin) [R].
3) Chronic Stress
Stress hormones from the HPA axis, such as CRH, can increase intestinal permeability and cause inflammation [R, R].
In 23 healthy volunteers, stress from giving a public speech increased gut permeability (via CRH) in those who also had increased cortisol [R].
Rats who experienced maternal separation in youth are also more prone to leaky gut when they experience social stress as adults [R].
4) Injury
29 intensive care patients showed increased intestinal permeability 72-96 hours after trauma. The more severe the injury, the greater the increase in gut permeability [R].
Also, intensive care patients with a large increase in intestinal permeability are at more risk of whole-body inflammation, multiple organ dysfunction, and infections [R].
Burn injuries caused leaky gut in both animals and humans [R].
Mice with burn injuries have disturbed microbiota (particularly a deficiency of butyrate-producing bacteria) and increased gut permeability [R].
5) Strenuous Exercise
Exercise can increase intestinal permeability. That is because, while we exercise, blood goes into the muscles and away from the stomach, and the supply of oxygen to the gut is reduced.
When the blood supply to the gut is reduced by more than half, intestinal permeability increases. For reference, people exercising at 70% maximum capacity have a 60–70% reduced blood flow to the gut. At 100% of maximum capacity the blood flow is reduced by 80% [R].
People who exercise at high intensities for longer periods have compromised gut barrier integrity. This puts them at a greater risk of chronic inflammation and diseases [R].
Running at 70% capacity increased intestinal permeability in 20 athletes, which is more pronounced in those who also already suffer from gut-related symptoms [R].
Cycling at 70% capacity increased gut leakiness and the amount of allergens reaching the bloodstream in 10 people [R].
Soldiers in high-intensity combat training have increased gut permeability as well as incidence and severity of gut-related symptoms [R, R].
However, in 11 well-trained athletes, the gut adapted to exercise. As a result, the intestinal permeability was not affected [R]. This suggests your gut barrier can be ‘trained’ as well as your muscles.
6) Alcohol
Alcohol can disrupt intestinal barrier function and increase gut permeability [R].
Alcoholics have higher gut permeability up to 4 days after drinking, sometimes even for up to 2 weeks [R].
One week of moderate consumption of red wine is safe in healthy people. However, it increased intestinal permeability in 14 patients with inactive IBD [R].
Some harmful bacteria, including E. coli, produce alcohol, which may be how these bacteria compromise the gut barrier function [R].
7) Bacterial Imbalance – Dysbiosis
The intestinal barrier acts as a shield which can be modified by gut bacteria [R].
Disturbances in the gut microbiota cause gut barrier dysfunction in various disorders and diseases [R].
A study of 100 overweight pregnant women showed that those with leaky gut (high zonulin) had a lower diversity of gut bacteria [R].
8) Infections
Many harmful bacteria gain access to the body by altering tight junctions to increase gut permeability [R].
Other types of infections also increase intestinal permeability, for example:
- Patients with malaria have increased intestinal permeability [R].
- Tapeworm parasites cause leaky gut in rats [R].
- Candida increases gut permeability (cell-based study) [R].
9) Inflammation
Inflammation increases intestinal permeability through TNF-alpha, IL-1beta, IFN-gamma, Nf-KB, and other cytokines [R, R, R, R].
10) Drugs, including NSAIDs and PPIs
Conventional NSAIDs increase gut permeability within 24h of ingestion. This is especially evident when they are taken long-term [R, R, R, R, R].
Stomach acid-suppressing drugs (PPI) also increase gut permeability [R, R]. However, in patients with cystic fibrosis, PPIs seem to reduce gut permeability [R].
11) Zinc Deficiency
Perturbed zinc balance is associated with abnormal gut permeability in children [R].
12) Vitamin Deficiency
Vitamins (especially A and D) are necessary for the proper function of the intestinal barrier since:
- Vitamin A-deficient diet impairs the intestinal barrier in rats [R].
- Vitamin D-deficient mice are more sensitive to gut barrier disruption [R, R, R].
13) Vitamin C
A study on 28 healthy female volunteers showed that Vitamin C may increase intestinal permeability and that this effect is additive when added to aspirin[R].
14) Iron
A study of 153 children showed that iron supplementation increased intestinal permeability [R].
15) Circadian Rhythm Disturbances
Circadian rhythms are important for the maintenance of the intestinal barrier [R].
A study of 22 night workers showed that they are more prone to alcohol-induced leaky gut [R].
Circadian disruptions, by either genetics or environmental cues, causes gut leakiness in mice. These mice are also more susceptible to further gut damage by alcohol [R, R].
16) Radiation
Exposure to radiation, such as in radiation therapy, increases intestinal permeability in humans [R, R].
Radiation rapidly disrupts tight junctions in mice and increases gut permeability in monkeys [R, R].
17) Chemotherapy
Chemotherapy increases intestinal permeability; however, the exact mechanism is still not fully understood [R, R, R, R].
18) Birth and Infancy
Babies naturally have a more leaky gut, which allows them to absorb immune substances from the mother’s milk [R].
19) Formula Vs. Breast-Feeding
Infants fed with formula have a more leaky gut than breast-fed infants [R].
A study on 62 preterm infants showed that those fed mostly human milk (>75%) had lower gut permeability than those receiving either low amounts or no human milk (<25%) [R].
20) Aging
The intestinal barrier may weaken as we age. Gut permeability (measured by zonulin) is higher in older people [R].
In 18 elderly people, high gut permeability was associated with higher TNF-alpha and IL-6. It was also associated with lower muscle strength and less habitual physical activity [R].
However, a study on 215 adults suggested that the gut barrier does not deteriorate with age per se. Instead, it deteriorated due to chronic inflammation and minor diseases that get more common as we age [R].
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