Leaky Gut: the Causes, Treatments, and How HMO Prebiotics Can Help

July 10, 2022 13 min read

Leaky Gut: the Causes, Treatments, and How HMO Prebiotics Can Help - Layer Origin Nutrition

Leaky Gut: What Causes it, How to Treat it, and How HMO Prebiotics Can Help

Leaky gut is a state of increased intestinal permeability, which occurs when the layer of epithelial cells that line the intestine becomes “leaky” and has growing gaps between the cells.

When the intestinal lining becomes impaired and leaky, toxins, pathogens, and too-big proteins can travel out of the gut into the bloodstream, purportedly causing health issues ranging from acne to arthritis to autoimmune diseases.

Although the science and clinical research backing up leaky gut syndrome is still relatively new to the gut health scene, many health practitioners are targeting this phenomenon as a way to improve both digestive and overall health.

In this article, learn more about what leaky gut is, the risk factors and leading causes behind it, how to treat it with diet and nutrition, and how consuming HMOs may help with leaky gut. 

What is Leaky Gut? A Look at Intestinal Hyperpermeability

Our intestinal walls are physical barriers that control what can enter the bloodstream to be used by other cells and tissues and what stays in the gut. This barrier is made up of a one-cell-thick layer of epithelial cells that are continuously renewed every four or five days.

These epithelial cells are sealed together by protein-rich tight junctions that act like sealants on a concrete wall that can remodel itself.

Tight junctions are essential for creating this physical barrier that allows water and nutrients to pass through but prevents toxins, pathogens, and proteins from going from our gut into the rest of our body.

Simply put, stronger tight junctions help maintain gut integrity. 

The gut lining also has a physical barrier made up of mucus, antimicrobial peptides, and immune cells.

These molecules create a sticky surface that traps and prevents the adherence of harmful pathogens or compounds to the epithelial cells. Mucosal barrier dysfunction is also a characteristic of increased intestinal permeability.

If our gut doesn’t keep up with both its cellular proliferation needs and tight junction seals, intestinal hyperpermeability, or leaky gut, can develop. Leaky gut is thought to cause widespread inflammation and potentially trigger immune reactions that can lead to skin, cognitive, digestive, and autoimmune disorders. 

What Are the Symptoms of Leaky Gut?

The most apparent symptoms of leaky gut are digestive-related, including bloating, gas, cramping, food sensitivities, intolerances, food allergies, constipation, and diarrhea.

Non-gastrointestinal symptoms of leaky gut are more challenging to pinpoint. Still, reports have linked leaky gut to neurological and neurodegenerative conditions, acne, obesity, metabolic syndrome, type 2 diabetes, migraines, chronic fatigue syndrome, thyroid abnormalities, mood disorders, and autism.

Clinical reports have also suggested that leaky gut contributes to autoimmune diseases, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and celiac disease.

However, it can be difficult to determine if leaky gut is a cause or symptom of any of these conditions.

Animal studies have determined that increased intestinal permeability occurs before the onset of some diseases, including type 1 diabetes, celiac disease, and irritable bowel syndrome, suggesting that leaky gut can, in fact, be the cause rather than the symptom. 

What Are the Risk Factors and Causes of Leaky Gut?

The risk factors and causes of leaky gut can be varied and wide-reaching, as medical professionals are still trying to figure out exactly what causes it.

The activation of a protein called zonulin is known to regulate leaky gut. Dysbiosis — an overabundance of bad bacteria in the gut — and gluten consumption in certain people are both known to trigger the release of zonulin.

Zonulin is a big protein that wedges between the tight junctions of epithelial cells, contributing to intestinal hyperpermeability.

While some health professionals think that eating gluten — the protein found in wheat, barley, and rye — can cause leaky gut in everybody, others believe that certain genetics make specific people susceptible to gluten-induced leaky gut.

There are multiple contributing factors behind leaky gut, including:

  • Obesity:Excess body weight or fat increases the “leakiness” of harmful bacteria like lipopolysaccharide (LPS), which diffuses through tight junctions to cause inflammation in the body.
  • Excessive alcohol consumption:Alcohol promotes gut dysbiosis and harmful bacteria overgrowth, causing an increase in endotoxin release — toxins produced by certain types of bacteria that can aggravate the gut lining.
  • Chronic stress:Stress, anxiety, and depression can all increase gut barrier permeability.
  • Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen
  • Inflammation:Chronic inflammation can be caused by many things, including obesity, alcohol consumption, chronic stress, and an unhealthy diet.
  • Gluten consumption in certain people will trigger zonulin to widen the gaps in the intestinal epithelium.
  • Other digestive conditions, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease.
  • Gut dysbiosis:An overgrowth of bad bacteria is a leading contributor to leaky gut.
  • Poor diet: This can include nutrient deficiencies and excessive sugar intake, as fructose can harm the barrier function of the intestinal wall.
  • Other diseases that can cause intestinal injury such as HIV/AIDS.
  • Chemotherapy and radiation therapies, both of which degrade the intestinal mucosa. 

How Do Doctors Diagnose Leaky Gut?

As leaky gut is not currently recognized as a medical diagnosis, there are no gold standards for diagnosing and treating it. However, there are some available tests that can support the existence of increased intestinal permeability, including:

  • Urine test (Also called themannitol and lactulose test):This test involves drinking a sugar-rich beverage, including some sugars called mannitol and lactulose that are not typically absorbed in the intestines. Scientists will then measure the sugar levels in your urine — if the mannitol and lactulose made it through the gut lining into the urine, that could indicate leaky gut.
  • Blood test:A blood test can analyze specific antibodies or endotoxins that are evidence of bacteria infiltration from the gut into the bloodstream.
  • Tissue biopsy:This invasive test takes a sample of intestinal tissue and puts it into something called an Ussing chamber, using electrical currents to measure the size of ions that transport across the gut barrier.
  • Confocal endomicroscopy:This is an endoscopy exam that lets doctors look at your intestinal lining with high resolution and magnification. They use a contrast liquid that will show up in the gut if there is increased intestinal permeability.
  • Zonulin test:Although some companies sell zonulin testing, it’s not entirely recommended, as it tends to have weak correlations with other intestinal permeability measures. For example, in studies linking elevated zonulin with various diseases, only a small fraction of those with the condition also had elevated levels of zonulin.

Future clinical research will need to determine which of these methods is best for diagnosing leaky gut. As for now, most practitioners believe that the urine test — sometimes called the mannitol and lactulose test — is the best, least invasive method for diagnosing increased intestinal permeability. 

What are the Current Treatments for Leaky Gut? 

Similar to the diagnosis of leaky gut, there is no gold standard for treating leaky gut due to a lack of medical acceptance and research.

However, as we will get into later in this article, targeting the root cause of the intestinal permeability is the first step in treating leaky gut.

This can include repopulating the gut with healthy bacteria, reducing inflammation, improving diet, treating digestive conditions with medications, and reducing stress.

Top Five Ways to Prevent Leaky Gut

There are several ways to approach the prevention of leaky gut, but most are rooted in supporting the intestinal barrier with nutrient-dense food or supplements.  

1. Prebiotics and Dietary Fiber

Prebiotics, for example, human milk oligosaccharides, can help to prevent leaky gut by providing fuel for intestinal cells in the form of short-chain fatty acids, strengthening the intestinal barrier, boosting healthy bacteria growth, and supporting immune cell functioning.

Other prebiotic carbohydrates — like some insoluble and soluble fibers — have also shown promise in treating leaky gut. Insoluble fiber includes cellulose, some hemicellulose, and lignin, while soluble fiber includes wheat dextrin, pectin, gums, beta-glucan, psyllium, and fructans, as well as some hemicellulose. Generally, only soluble fibers can be processed by gut bacteria into SCFAs.

However, although all prebiotics are fiber, not all fibers are also prebiotics. While fiber can be found in all plant foods, prebiotics only occur in certain foods, like leeks, apples, asparagus, chicory, Jerusalem artichokes, garlic, and onions.

In one study published in the journal Nutrients, people who increased their daily fiber intake from 19 grams to 29 grams had significantly reduced zonulin levels over the six-month study.

It’s thought that soluble fiber especially helps leaky gut because the intestinal fermentation of soluble fiber boosts butyrate production, which we know strengthens intestinal barrier function. 

2.  Dietary or Supplemental Probiotics

Probiotics are helpful bacteria that reside in the gastrointestinal tract and impart benefits to human health. As dysbiosis in the gut is thought to be a risk factor for developing leaky gut, improving the diversity and makeup of gut microflora may prevent impaired intestinal permeability.

In a May 2020 study, researchers from the Wake Forest School of Medicine in North Carolina found evidence that probiotics can benefit leaky gut in mice. They used a probiotic mixture containing five Lactobacillus and five Enterococcus strains that were all isolated from a healthy infant gut.

This probiotic cocktail prevented leaky gut and reduced gut dysbiosis, inflammation, and metabolic dysfunction in aged mice. The probiotics primarily worked by increasing tight junctions between epithelial cells.

Probiotic supplements have also been shown to be beneficial for other digestive disorders, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, which could help prevent or improve leaky gut by reducing those gastrointestinal symptoms.

In addition to probiotic pills, increasing dietary probiotics can boost the diversity of beneficial bacteria in the microbiome. Dietary probiotics are found in fermented foods, including sauerkraut, kimchi, yogurt, natural pickles, miso, natto, tempeh, kombucha, and kefir.

3. Maintaining a Gluten-Free Diet

Although this may not work for everybody, a gluten-free diet is thought to improve leaky gut in people with high genetic susceptibility. This is because gluten can trigger zonulin release, which wedges between intestinal epithelial cells and weakens the gut lining.

In a study by researchers from the University of Manitoba, 87% of people with celiac disease who adopted a gluten-free diet had normalization of their intestinal permeability after one year.

Conversely, people who consumed even trace amounts of gluten had increased markers of leaky gut at the next visit.

4. Nutrient-Dense, Antioxidant-Rich, and Anti-Inflammatory Foods

Consuming a diet rich in anti-inflammatory and nutrient-dense foods can help to prevent leaky gut. Nutrient-dense foods are low in calories and rich in vitamins, minerals, antioxidants, and healthy fats.

This is opposed to caloric-dense foods, which have high amounts of calories with low quantities of vitamins, minerals, and nutrients.

Nutrient-dense foods tend to go hand-in-hand with anti-inflammatory foods, including:

  • Fruits: Berries, apples, pears, pomegranate, and citrus fruit are all high in antioxidants and polyphenols.
  • Vegetables: Dark leafy greens, cruciferous vegetables (broccoli, kale, Brussels sprouts, cauliflower), and orange or red-colored vegetables are some of the healthiest types.
  • Fish and seafood:Salmon, mackerel, anchovies, tuna, and sardines are especially rich in omega-3 fatty acids, which are essential for modulating inflammation.
  • Eggs:The egg white is rich in protein, while the yolk has plentiful amounts of healthy fat, choline, and other nutrients.
  • Lean meat and poultry:Chicken, turkey, venison, and some pork, lamb, and beef are all lean meat options.
  • Nuts and legumes:All types of nuts, beans, and lentils are high in fiber and protein.
  • Herbs and spices:All herbs and spices are healthy, especially oregano, rosemary, turmeric, ginger, garlic, cinnamon, parsley, cloves, saffron, and basil.
  • Antioxidant-rich beverages: Coffee, tea, and small amounts of red wine are loaded with beneficial antioxidants, including chlorogenic acid in coffee, epigallocatechin gallate in green tea, and resveratrol in red wine.

These foods can provide plenty of antioxidants, polyphenols, vitamins, minerals, and healthy fats to support strong intestinal barrier function and gut microbe diversity.

5. Limit or Avoid Inflammatory Food and Drinks

On the flip side, limiting or avoiding foods, drinks, and medications that trigger inflammation can help to prevent leaky gut. 

Western-style diets — which are high in salt, sugar, saturated fat, and refined carbohydrates — alter gut bacteria composition and reduce beneficial bacteria, including Bifidobacterium.

There are many inflammatory foods, beverages, or medications that can disrupt both the gut microbiome and the intestinal lining, including:

  • Processed foods high in refined carbohydrates, fat, or sugar, including fast food, chips, crackers, candy, desserts, white bread, and sweets
  • Fried food
  • High-fructose corn syrup
  • Alcohol
  • Smoking cigarettes
  • Conventional red meat
  • Unhealthy fat, like trans fats, margarine, shortening, lard, and omega-6 seed oils, including canola, vegetable, and soybean oil.
  • NSAIDs
  • For some people, gluten and dairy can be inflammatory.

HMO Prebiotics for Leaky Gut

One way to improve leaky gut — and help with other digestive conditions at the same time — may be with HMOs. HMO is a type of sugar abundant in human breast milk. HMOs are non-digestible carbohydrates that travel to the large intestine and can benefit gut, immune, and cognitive health.

There are several ways that HMOs may help to prevent or improve symptoms of leaky gut, including strengthening the intestinal barrier, boosting short-chain fatty acid and Bifidobacteria and possibly Akkermansia production, and supporting immune function.

HMOs Strengthen the Intestinal Barrier with Short-Chain Fatty Acids

HMOs can help reduce or prevent leaky gut by providing fuel for the cells that line our intestines in the form of short-chain fatty acids, whichstrengthens the intestinal barrier.

Short-chain fatty acids (SCFAs) are beneficial compounds produced when our gut bacteria feed on prebiotics like HMOs. The three most abundant SCFAs are acetate, propionate, and butyrate, with butyrate providing the most health benefits.

Higher SCFA production is associated with a lower prevalence of leaky gut because butyrate can strengthen the tight junctions between epithelial cells, as seen in this study published in the Journal of Nutrition.

Butyrate maintains the health of intestinal cells called colonocytes by providing them with energy, contributing to the integrity of the gut lining. Butyrate is also thought to induce the production of mucin — a key component of mucus that acts as a chemical barrier against pathogens.

SCFAs also have important immune-modulating activity, which can be beneficial for improving leaky gut syndrome.

HMOs Support Healthy Gut Bacteria Growth

HMOs may also help with leaky gut by improving the makeup of bacteria in our guts, primarily by boosting Bifidobacteria production.

The genus of bacteria called Bifidobacteria encompasses some of the most beneficial members of the gut microbiome. People with irritable bowel syndrome, inflammatory bowel disease, obesity, and type 2 diabetes tend to have lower levels of this bacterial genus.

Bifidobacteria are the most abundant bacteria in the gut shortly after birth. However, levels of this bacteria decline with age, so it becomes essential to boost Bifidobacteria content through diet or supplements like HMOs.

One specific type of Bifidobacteria called Bifidobacterium longum sub spp.infantis boosts the production of tight junction proteins that prevent leaky gut and keep our intestinal barrier lining strong.

However, B. infantis needs to feed on prebiotics, like HMOs, for this to occur. Without this fuel, these beneficial bacteria can’t survive.

HMOs Improve Immune System Functioning

The gut microbiome and the immune system are intricately linked by a secondary lymphatic organ called gut-associated lymphoid tissue (GALT), which protects the body from pathogens but allows tolerance to healthy bacteria.

HMOs may directly modulate immune responses by preventing the adhesion of pathogens to the intestinal lining, thereby strengthening the mucosal barrier.

HMOs prevent pathogenic adhesion by acting as a “decoy” receptor for unhealthy bacteria, like E.coli.

These unique prebiotics have also been shown to reduce the activity and expression of inflammatory cytokines, like interleukin-4 (IL-4), while increasing the expression of anti-inflammatory cytokines like interleukin-10 (IL-10) and interferon-gamma (IFN-γ).

HMOs may benefit the immune system by boosting SCFA production. Short-chain fatty acids increase the activity of beneficial immune cells like T helper cells, macrophages, neutrophils, and natural killer (NK) cells.

These immune functions suggest that HMOs are involved in regulating the innate immune system against infection. As dysregulated immune responses can cause leaky gut, HMOs may be able to help modulate immune activity and prevent increased intestinal permeability.

Key Takeaway 

  • Leaky gut — also known as increased intestinal permeability — is a condition in which the cells lining the intestinal wall “loosen” or grow gaps between them, allowing proteins and bacteria to escape from the gut into the bloodstream.
  • Leaky gut has been implicated in many health conditions, both digestive and non-gastrointestinal.
  • HMO prebiotics may help to prevent leaky gut or improve its symptoms. HMOs strengthen the intestinal barrier, increase short-chain fatty acid production, support immune functioning, and boost healthy bacteria growth.
  • Other ways to prevent or treat leaky gut include consuming a diet high in prebiotics, probiotics, dietary fiber, antioxidants, polyphenols, and healthy fats.
  • Avoiding inflammatory foods, reducing stress, limiting alcohol consumption, and maintaining a healthy body weight can also help to prevent leaky gut.


Written By: 

Cambria Glosz, Registered Dietitian 

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