‘Leaky gut’ is gaining more attention by the day, although it is not a recognized medical condition. Certain dietary and lifestyle choices are associated with increased or decreased intestinal permeability. Read on to learn more about them.
What Is Leaky Gut?
The theory is fairly simple. When there are abnormalities in the intestinal barrier, the intestinal permeability increases. This potentially means that more of the gut content can pass/leak through, which is referred to as “leaky gut” .
Some scientists think that when the gut is leaky, gut bacteria and their products may escape the gut, which could potentially produce inflammation and cause tissue damage. Similarly, food-derived antigens (proteins or partially digested proteins) could pass through the gut and promote both local or whole-body immune responses .
To learn more about what makes the gut “leaky” and the conditions associated with it, check out this post.
How to Prevent a Leaky Gut
As leaky gut may occur as a symptom in a number of underlying diseases, the most important thing is to work with your doctor to address any potential underlying health condition.
For example, several studies have shown that chronic infections can increase gut permeability, and therefore they need to be addressed if possible [2, 3, 4, 5, 6].
Some clinical studies show that addressing leaky gut may be beneficial in some gut-related conditions such as inflammatory bowel disease (IBD), diarrhea, irritable bowel syndrome (IBS), and celiac disease. However, at this point in time, there is little to no clinical evidence that addressing leaky gut could improve any particular non-gut related condition.
1) Potentially Beneficial Lifestyle and Dietary Changes
Much of the emerging research shows that stress may increase intestinal permeability [7, 8, 9]. Managing stress levels is one way to potentially improve the function of your intestinal barrier and your overall health.
A healthy circadian rhythm may also help keep your gut healthy .
Alcohol increases intestinal permeability and is best avoided if you have gut issues [11, 12, 13]. Even moderate consumption can increase intestinal permeability in people who have gut inflammation .
If you have certain food sensitivities (e.g. gluten), you may need to avoid offending foods. However, make sure your diet is overall healthy and well balanced, to avoid nutritional deficiencies .
2) Moderate Exercise
In 30 people with diabetes who initially had increased intestinal permeability, 6 months of regular exercise improved leaky gut and decreased low-grade inflammation .
Swimming increased tight junction protein levels in rats .
In mice, 30 minutes of swimming per day maintained low intestinal permeability. It also prevented chronic stress-induced gut barrier dysfunction .
3) Vitamins and Minerals
Make sure you are not deficient in vitamins and minerals required for proper gut barrier and immune function. These include vitamin A (retinol), vitamin D, zinc, and B vitamins.
A clinical trial in 79 children showed that vitamin A lowered intestinal permeability .
Vitamin D helps maintain the intestinal barrier [20, 21, 1].
Vitamin D helped maintain low intestinal permeability in a study with 27 Crohn’s disease patients in remission .
Vitamin D also reduced the sensitivity of the intestinal barrier to alcohol in mice .
Niacin (vitamin B3) decreased intestinal permeability in patients with alcohol-induced niacin deficiency .
Zinc restored intestinal permeability in Crohn’s disease patients, probably by maintaining tight junctions [25, 26].
In 12 Crohn’s disease patients in remission, those receiving zinc (10 patients) had normal gut permeability and did not relapse. Of the remaining 2 who had increased intestinal permeability, 1 relapsed .
Low levels of zinc improved intestinal permeability in a study of 58 children with diarrhea .
Probiotics may help reduce gut leakiness. Some scientists suggest they can strengthen tight junctions and restore the integrity of the intestinal barrier.
In 2 studies with 10 and 7 people, respectively, L. plantarum promoted gut barrier repair and increased the stability of tight junctions [28, 29].
Fermented milk with probiotics decreased gut permeability in a clinical trial with 30 IBS patients . The probiotics included S. thermophilus, L. bulgaricus, L. acidophilus, and B. longum.
The following probiotics have helped improve ‘leaky gut’ in animal and cell studies:
- Lactobacillus rhamnosus GG [31, 32, 33, 34]
- L. acidophilus and Streptococcus thermophilus 
- L. plantarum [36, 37, 38]
- L. paracasei 
- L. gasseri 
- Bifidobacterium infantis 
- L. helveticus and B. longum 
- L. plantarum and L. reuteri 
- Bacteroides fragilis (improved autism-related symptoms in mice) 
- Escherichia coli Nissle 1917 
Prebiotics are fibers that stimulate the growth of beneficial bacteria in the gut.
Inulin-enriched pasta preserved the intestinal barrier and decreased zonulin in 20 healthy volunteers .
In 32 people with fatty liver, a diet high in fiber reduced intestinal permeability and blood zonulin levels and improved liver function .
Prebiotic galactooligosaccharides (GOS) improved intestinal barrier function in rats with pancreatitis .
Prebiotics lowered intestinal permeability and improved tight-junction integrity in obese and diabetic mice .
Studies suggest that glutamine may help maintain intestinal barrier function .
Glutamine had beneficial effects on intestinal integrity in 101 preterm infants and increased intestinal barrier function in a study with 80 malnourished children [51, 52].
A study of 51 cancer patients showed that glutamine countered the chemotherapy-induced increase in intestinal permeability .
Glutamine reduced radiation-caused gut injury and maintained lower gut permeability in rats .
No clinical evidence supports the use of any of the below-listed foods and supplements for improving gut permeability. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
- Fermented foods (barley, soybean, kimchi) decreased gut permeability in mice and rats with IBD-like inflammation [55, 56, 57]
- Omega-3 acids helped improve gut barrier function in mice with inflammation and after chemotherapy [58, 59]
- Curcumin improved gut barrier function in rats, mice, and human cells [60, 61, 62, 63].
- Butyrate helped protect the intestinal barrier in rats with gut inflammation, and in mice fed a high-fat diet or exposed to chemotherapy [64, 65, 66].
- Melatonin improved gut barrier function in diabetic rats and rats on alcohol and in mice with IBD-like gut inflammation or mice treated with NSAIDs [67, 68, 69, 70, 71].
- Ginkgo biloba helped restore the gut barrier in rats by restoring tight junctions .
- Lipoic acid supplementation reduced intestinal permeability in post-weaning rats .
- Quercetin protected the intestinal barrier from NSAID-induced damage in rats [74, 75].
- Sulforaphane, found in high amounts in broccoli sprouts, strengthened the gut barrier in mice .
Genetic Factors That Influence Intestinal Permeability
HLA-DQ2.5 and HLA-DQ8.1
HLA-DQ is a protein found on the surface of cells that communicate with the immune system (it presents antigens to immune cells).
Studies suggest that two variants, HLA-DQ2.5 and HLA-DQ8.1 are associated with about 6-fold higher risk of developing celiac disease. About 98% of people with celiac disease have one or both of these variants [77, 78, 79].
You have HLA-DQ2.5 if you have the following variants:
You have HLA-DQ8.1 if you have the following variants:
- The HLA-DQA1*0301 variant in the HLA-DQA1 gene
- The HLA-DQB1*0302 variant in the HLA-DQB1 gene
Don’t panic if you have one of these variants. It’s important to stress that up to 40% of the general population has these variants. However, only about 1% go on to develop celiac disease. This indicates that HLA-DQ2.5 and HLA-DQ8.1 variants may be necessary but not sufficient for disease development [80, 79, 81].
Because of this, the primary value of genetic testing is to rule out celiac disease/gluten intolerance. If you are among the 60% of people who do not carry either of these variants, you are unlikely (>95%) to be at risk. That means that you can avoid unnecessary invasive test procedures, such as blood punctures, duodenal biopsies, etc. .
Apart from celiac disease, studies suggest that having either HLA-DQ2 or HLA-DQ8 is associated with an increased risk of type 1 diabetes, with a higher risk for people who carry both variants [82, 83].
Myosin IXb (MYO9B) is a protein that helps maintain the intestinal barrier. Based on a study in 1.6k Europeans, these MYO9B variants have been associated with increased intestinal permeability :
Three of these variants have also been associated with IBD: rs1545620, rs1457092, and rs2305764, based on a meta-analysis of 10 studies with 8.9k cases, and 9.4k controls .
The rs1545620 and rs2305764 variants have been associated with celiac disease in multiple studies [86, 87, 88, 89]. However, there is also a study that failed to find an association between MYO9B and celiac disease .
rs2279003 and rs2305764 have also been linked with type 1 diabetes, while rs1457092 was associated with lupus and rheumatoid arthritis [91, 88].
NOD2 (also known as CARD15) functions as an “intestinal gatekeeper.” This protein recognizes bacteria, viruses, and parasites, and activates the immune system. It also helps shape our gut microbiota .
Based on one study that involved people with Crohn’s disease, their relatives, and healthy controls, these NOD2/CARD15 variants were more often found in people with Crohn’s disease and their relatives :
The same study showed that in healthy relatives of Crohn’s disease patients, 40% of those with the 3020insC and 75% of those with both 3020insC and R702W had increased intestinal permeability .
3020insC (either rs2066847 or rs5743293) was also associated with increased permeability in another study with Crohn’s disease patients .
Janus kinase-2 (JAK2) promotes the growth and division of cells, in response to hormones and cytokines (interferon, erythropoietin, leptin, and growth hormone) .
IBD patients carrying the rs10758669 (C) variant more often had increased intestinal permeability, based on a study in 464 Crohn’s disease patients, 292 ulcerative colitis patients, and 508 controls .
HP is the haptoglobin gene. Haptoglobin binds free hemoglobin in the blood and prevents it from causing oxidative stress and tissue damage. It comes in 2 common variants: Hp1 and Hp2.
It was discovered that prehaptoglobin-2, a precursor of the Hp2 variant, is actually zonulin [97, 98].
Therefore, people with Hp2 variants may have an increased risk of immune and inflammatory disorders due to higher zonulin and increased intestinal permeability .
MAGI2, MAGI3, and PARD3
MAGI2, MAGI3, and PARD3 are tight junction proteins.
IBD has been associated with rs6962966 in MAGI2 and rs1343126 in MAGI3 .
rs10763976 in PARD3 and rs6962966 in MAGI2 have been associated with both celiac disease and ulcerative colitis .
AHR (aryl hydrocarbon receptor) is a protein that activates detoxification enzymes in response to pollutants and cancer-causing agents. It also plays an important role in activating the immune system [101, 102].
A study suggests that AHR rs7796976 (G) may increase the risk of disturbed intestinal permeability in Crohn’s disease patients. Smoking can exacerbate this effect .
Leaky gut is the name given to a condition in which the intestinal barrier allows potentially harmful compounds to cross into the bloodstream. It is not a universally accepted medical condition, but rather a speculative explanation for a suite of symptoms.
A healthy lifestyle, exercise in moderation, and a balanced diet rich in fiber may help improve gut health. Certain genetic factors also appear to influence intestinal barrier function, and strategies tailored to DNA may be considered.