Leaky gut syndrome, also known as increased intestinal permeability, is a condition where the lining of the small intestine becomes damaged and develops tiny holes or spaces that allow undigested food particles, bacteria, and toxins to leak through into the bloodstream. This can trigger inflammation and changes in the immune system. There are a few key toxins and factors that can contribute to leaky gut syndrome.
Zonulin
One of the main toxins involved in increasing intestinal permeability is zonulin. Zonulin is a protein that modulates the tight junctions between epithelial cells of the small intestine. When zonulin levels are elevated, these tight junctions loosen, allowing for increased intestinal permeability (leaky gut).
Some potential causes for increased zonulin production include:
- Dysbiosis – Imbalance in gut microbiome
- Gluten exposure – Especially in those with gluten sensitivity
- Enteric infections – Bacterial or viral gastrointestinal infections
- Stress
- Environmental toxins like mold, mercury, or BPA
Reducing zonulin levels through a gluten-free, low-sugar diet and healing the gut microbiome can help reverse leaky gut syndrome.
Lipopolysaccharide (LPS)
Lipopolysaccharide (LPS) is an endotoxin found on the outer membrane of gram-negative bacteria that can trigger leaky gut. With increased intestinal permeability, LPS can cross from the intestinal lumen into the bloodstream leading to systemic inflammation. High levels of circulating LPS have been associated with:
- Obesity
- Insulin resistance
- Type 2 diabetes
- Heart disease
- Alzheimer’s disease
- Parkinson’s disease
- Autism
- Depression
LPS triggers inflammation through activating immune cells like macrophages to release inflammatory cytokines like TNF-alpha, IL-1beta, IL-6.
Strategies to lower LPS levels include:
- A low-fat diet
- Increase prebiotics to support healthy gut flora
- Take binders like cholestyramine, charcoal, or gluten-free silymarin
- Heal integrity of gut lining
Glyphosate
Glyphosate is the main chemical in the herbicide Roundup. Traces of glyphosate can be found in many food products as well as cotton clothing and sanitary products. Glyphosate has been shown to damage the tight junctions between gut epithelial cells, allowing for leaky gut.
A study on chickens given feed contaminated with glyphosate showed significantly increased intestinal permeability within two weeks. Rats fed Roundup and glyphosate for two years had signs of leaky gut activation.
Glyphosate may increase gut permeability by:
- Acting as a antibiotic against beneficial gut bacteria like Lactobacillus
- Depleting glutathione levels needed for antioxidant defense
- Interfering with cytochrome P450 enzymes involved in detoxification
Eating organic foods as much as possible and avoiding GMO crops sprayed with Roundup can help minimize glyphosate exposure and effects on the gut lining.
Gluten
Gluten is a protein found in wheat, barley, and rye that has been linked to leaky gut in those with celiac disease or gluten sensitivity. Gliadin, a component of gluten, has been shown to increase zonulin release and directly damage intestinal tight junctions.
A study found that exposure to gliadin triggered zonulin release and increased gut permeability within 30 minutes in patients with celiac disease. Studies also show that those with non-celiac gluten sensitivity experience leaky gut when consuming gluten.
Those with celiac disease or gluten sensitivity should follow a strict gluten-free diet to help reverse leaky gut symptoms. For those without gluten issues, limiting gluten-containing foods may still be beneficial for reducing intestinal permeability.
Stress
Psychological stress can also contribute to leaky gut by increasing inflammation and oxidative stress in the intestinal lining. The stress hormone cortisol may negatively impact gut barrier function.
Studies show that various types of stress like early life trauma, prolonged anxiety, depression, or PTSD can increase intestinal permeability and lead to higher circulating LPS levels.
Chronic work stress was associated with decreased expression of tight junction proteins and increased permeability. Stress management through meditation, yoga, counseling, or relaxation techniques may help.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Common over-the-counter NSAIDs like aspirin, ibuprofen, and naproxen have been shown to increase intestinal permeability and permeability when taken regularly.
One study found that indomethacin and naproxen increased small intestine permeability after just 7 days of administration in healthy volunteers. Another study showed disruption of tight junctions in the gut lining of patients taking NSAIDs.
Limiting NSAID use, choosing alternative pain medications when possible, and healing the gut lining after NSAID use can help reverse this effect.
Infections
Certain bacterial, viral, and fungal infections in the gastrointestinal tract can damage the intestinal lining and cause leaky gut symptoms. Common examples include:
- SIBO – Small intestinal bacterial overgrowth involves excessive bacteria growth, often from too few beneficial bacteria that produce short-chain fatty acids needed for gut barrier integrity.
- Candida – Candida yeast overgrowth stresses the immune system and may penetrate the intestinal wall.
- Parasites – Giardia lamblia, blastocystis hominis, Cryptosporidium can lead to villous atrophy and damage to tight junctions.
- Viral gastroenteritis – Rotavirus, norovirus gastroenteritis erodes gut barrier and increases permeability.
Treating underlying infections through antimicrobials or probiotics along with following a gut-healing diet can help reverse leaky gut associated with pathogens.
Alcohol
Excessive alcohol consumption is known to significantly increase gut permeability and allow bacteria and endotoxins to cross into the bloodstream. This can even occur after a single binge drinking episode.
Binge drinking has been shown to cause a spike in blood endotoxin levels as the gut lining becomes more permeable. Chronic alcoholics often have systemic inflammation and high endotoxemia.
Alcohol likely damages the intestinal barrier through:
- Increasing oxidative stress
- Depleting glutathione
- Altering gut microbiota
- Interfering with tight junction proteins like zonula occludens-1 (ZO-1)
Limiting alcohol intake and allowing time for gut healing after alcohol consumption can help reverse alcohol-induced leaky gut. Glutamine supplements may also help repair alcohol associated hyperpermeability.
Certain Medications
In addition to NSAIDs, some medications have also been associated with increasing gut permeability, especially when used long-term. These include:
- Antibiotics – antibiotic overuse promotes gut dysbiosis and can damage microbiome diversity needed to support the intestinal barrier.
- Proton pump inhibitors (PPIs) – reduce stomach acid needed to protect against bacterial migration.
- Hormonal contraceptives – may alter gut flora populations and affect permeability.
- Chemotherapy – can damage rapidly dividing cells in intestine lining.
When taking any medication long-term, it is important to support gut health through diet, supplements, and repairing microbial balance. Work with your doctor to determine if alternative options are available.
Environmental Toxins
Toxins encountered in the environment such as heavy metals, mold, pesticides, and industrial chemicals have been shown to impact intestinal permeability as well.
Arsenic exposure allows bacteria like E.coli to penetrate the intestinal wall by impacting tight junction proteins. Organophosphate pesticides can also alter gut permeability and increase inflammatory cytokines.
Reducing toxin exposures through an organic, unprocessed diet, using green cleaning and personal care products, and addressing mold issues can help minimize toxin related leaky gut effects.
Lectins
Lectins are carbohydrate-binding proteins found in many plants, especially grains, legumes, and nightshade vegetables. Some lectins resist digestion and may bind to intestinal cells, causing damage to the brush border and promoting leaky gut.
Plants contain lectins as a defense mechanism against insects and pests. But for sensitive individuals, regular exposure can trigger leaky gut, IBS symptoms, and inflammation.
Those with autoimmunity or lectin sensitivity may need to restrict or limit dietary lectin sources such as:
- Grains – wheat, quinoa, rice, oats
- Legumes – soybeans, kidney beans, peanuts
- Nightshades – tomato, potato, eggplant
Traditional preparation techniques like soaking, sprouting, fermenting, and cooking can help reduce lectins in foods as well.
Dairy
While dairy is not necessarily a toxin, many people have difficulty properly digesting dairy products due to lactose intolerance or casein sensitivity. For these individuals, dairy proteins and sugars can negatively impact the intestinal barrier.
Studies show that lactose can increase intestinal permeability and activate immune responses in those lacking sufficient lactase enzyme levels to break it down. Beta-casomorphin-7, a peptide found in casein, has also been shown to increase gut permeability.
Testing for lactose intolerance and casein sensitivity can help determine if dairy is a contributor to leaky gut symptoms. Eliminating dairy for 30 days and then reintroducing to assess symptoms is another option.
Gut Dysbiosis
Imbalances in the gut microbiome between beneficial and potentially pathogenic bacteria can promote leaky gut as well. Having insufficient beneficial bacteria impairs the integrity of the gut barrier.
Probiotic bacteria like Lactobacillus and Bifidobacterium species help strengthen tight junctions and reduce gut permeability. They also lower inflammatory responses to endotoxins.
On the other hand, having an overgrowth of bacteria like E. coli, Klebsiella, and Pseudomonas aeruginosa has been associated with increased gut permeability and endotoxin translocation.
Restoring balance through probiotic foods, fermented foods, and strategic probiotic supplementation can help reverse dysbiosis and leaky gut.
Diet High in Sugar and Unhealthy Fats
A diet high in sugar, refined carbohydrates, processed foods, and saturated or trans fats provides a breeding ground for unhealthy bacteria to proliferate. This can crowd out beneficial species important for maintaining the gut barrier.
High fat meals have also been shown to result in higher circulating endotoxin levels, even in healthy individuals. Long-term diets low in fiber and antioxidants can also impair the protective intestinal mucus layer.
Shifting to a whole foods diet focused on fiber-rich plant foods, beneficial fats, and lean proteins provides nutrients needed for gut barrier function. Limiting sugar feeds healthy bacteria.
Certain Food Additives
Certain emulsifiers and food additives common in processed foods have also been shown to impact the mucus layer and increase gut permeability when consumed regularly.
In studies, additives like polysorbate 80 and carboxymethylcellulose promoted bacterial translocation across the intestinal wall and induced low-grade inflammation.
Avoiding heavily processed foods with additives as much as possible and making fresh, whole foods the foundation of your diet can help minimize negative effects.
Key Takeaways
- Zonulin, LPS, and gluten are some of the primary toxins that can trigger leaky gut by damaging tight junctions in the intestinal lining.
- Glyphosate, infections, alcohol, certain medications, and environmental toxins are other contributing factors.
- Diet and lifestyle factors like chronic stress, food additives, and poor gut health also play a role.
- Removing sources of gut irritants and following a leaky gut diet and lifestyle regimen can help reverse permeability.
- Supporting the gut microbiome, managing stress, and reinforcing tight junctions are key recovery strategies.