Top 10 Causes of Leaky Gut (And How to Avoid Them): An Evidence-Based Guide
- Sasha Elizar, M.S.
- Apr 17
- 21 min read
We all know gut health is the foundation of an optimized body. Like soil nourishing the roots and branches of a tree, nutrition feeds the gut and organs of the body. The richer the nourishment, the lusher the leaves: skin, muscles, hair, nails, vision, etc. Thus, supporting the roots (that is, the gut) allows you to absorb more light (i.e., gain more energy, vitality, and clarity, and enjoy more life) and also give more shade to others (i.e., emanate generosity, presence, and make a positive impact). Stronger roots make for a taller tree.
For the past 10 years as a neuroscience researcher, I have been interested in the causes of human pain, suffering, and disease. Although self-regulation and stress reduction (e.g. an information diet) are major aspects of mental well-being, it has become increasingly evident that in long-term, brain function relies heavily on lifestyle factors, particularly nutrition. Nutrition is a particularly bio-hackable and modifiable factor in health: daily choices add up to our body composition, rate of aging, function, and quality of life. Disease is driven by inflammation, and improper nutrition majorly contributes to inflammation.
What’s one of the most significant drivers of inflammation? Leaky gut, a condition which is now widely acknowledged within the scientific community. This article explores in depth what causes leaky gut, an important pre-requisite to any discussion about solutions to leaky gut.
Your gut barrier is made up of mucus and a single layer of intestinal epithelial cells. (Learn more about gut layer anatomy.) Leaky gut is a process whereby small gaps in the gut lining allow food contents, microbes, and microbial signatures to “leak” into immune tissue and circulation. Gut inflammation can create a ripple effect beyond the GI tract, affecting the skin, brain, lungs, immune system, metabolism, and the heart, bringing symptoms like pain, anxiety, depression, breakouts, brain fog, fatigue, vitamin deficiencies, asthma, and autoimmune disease.
Disease is often rooted in inflammation; in turn, a major driver of inflammation is leaky gut. We turn our attention now to the root causes of leaky gut. In this feature we will cover the host, psychological, biological, dietary, chemical, and electromagnetic causes of leaky gut.
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What are the signs and symptoms of leaky gut?
How does one come to suspect they may have leaky gut? Symptoms of leaky gut include:
Abdominal pain and cramps
Irritable bowel syndrome (IBS)
Bloating (often driven by small intestinal bacterial overgrowth, or SIBO)
Diarrhea
Fatigue
Gas
Headaches
Food allergies and sensitivities
These symptoms don’t necessarily mean someone has leaky gut, but it’s worth checking through functional gut panels [1] (see biomarkers of leaky gut). One of biggest leaky gut red flags is trouble digesting a variety of foods.
Leaky gut can also have far-reaching effects on other body symptoms, generating hormone disruption, low energy, brain fog, inflammation, dysregulated metabolism, and skin concerns, as discussed in the biomarker issue.
What causes gut dysbiosis? What are the effects of gut dysbiosis?
The best way to prevent leaky gut is to prevent gut dysbiosis from happening in the first place, wherever possible, by cultivating a balanced gut ecosystem. Gut dysbiosis is an imbalance in the composition and function of the gut microbiota, towards a more pathogenic, pro-inflammatory phenotype. That is, there is a greater proportion of harmful microbes that secrete deleterious metabolites, which have a negative effect on a host’s physiology.
Sometimes, temporary changes in the microbiota are unavoidable, such as dietary changes due to travel or antibiotic use due to infection. However, sustained gut microbial imbalances increase risk of leaky gut.
The gut microbiota can be thrown off balance by a high fat diet, nutritional insufficiency (e.g., fiber or tryptophan deficiency), pesticides on food, sedentary lifestyle, stress, poor sleep [2], and antibiotic use [3].
Gut dysbiosis may lead to malabsorption of nutrients, vitamins, and minerals; insulin resistance; and compromised immunity [2, 4]. Eubiosis, indicated by favorable metabolic activity in the gut, goes a long way towards building and maintaining a balanced, healthy body.
Outline: Top 10 Causes of Leaky Gut
Aging
One study compared older and younger female monkeys that fed an identical, controlled diet. They found that lipopolysaccharide binding protein 1 (LBP-1), a biomarker of leaky gut, was five times higher in the older monkeys than the younger, diet-matched controls [5]. This suggests that leaky gut occurs due to the natural aging process.
As we get older, we have a decreased ability to fight infection. Fortifying the gut-associated lymphoid tissue (GALT) and eating an anti-inflammatory diet can both go a long way to preserving gut function. Microbiome rejuvenation therapy is also in early stage investigations for its potential to reverse some of the declines in function of the gut with age.
Genetics and Family History
Asymptomatic close relatives of patients with inflammatory bowel diseases (IBDs) also show compromised barrier integrity [6]. IBS is more common in individuals with a first-degree relative with IBD, and IBS is associated with leaky gut. Indeed, there is an inherited component of leaky gut, but whether it is at the level of genetics or epigenetics is unclear. These distinctions can lead to variation in disease severity and manifestation.
Certain food intolerances (e.g. gluten intolerance) may have some genetic influence. Some people have an impaired ability to digest gluten because they just don’t have enough digestive enzymes to deal with the extraordinarily high levels of gluten in our food today. Indeed, the levels of added gluten in food tripled in the US from 1977 to 2012.
[Learn more about other host-related causes of leaky gut—autoimmune disease, inflammation, and oxidative stress—in our full report.]
Stress (Mental and Physical)
The mind-body connection is very real—mental states influence health and disease. Chronic stress modulates inflammation and can drive leaky gut. Through the hypothalamic-pituitary-adrenal (HPA) axis, stress changes blood flow, triggers mast cells [7], weakens the mucus lining of the gut [8], and speeds up GI motility [9].
Gut microbiota also impact corticotropin releasing hormone (CRH) secretion, influencing stress hormone signaling. Thus, stress reduction and emotional regulation practices can be paired with gut microbiota modulation, most prominently through dietary protocols and probiotics, which have shown to be beneficial for depression and memory.
Traumatic brain injury (TBI) [10, 11], nightshift work [12], intense exercise [13-15], high altitude [16], and heat stress [17-19] can all increase epitestinal epithelial barrier permeability as well.
[For more details on the impact of stress, trauma, depression, and physical overexertion on gut function, including mechanisms, download the full report.]
Dietary Factors
The Western Diet, Vitamin and Nutrient Deficiencies, Malabsorption, and the State of American Nutrition
Conventional agriculture practices are depleting our food’s nutrition, causing endemic vitamin and nutrient deficiencies and modern malnutrition. High yield practices [20] and pesticide application kill soil microbes and fungi and diminish the nutritional quality of crops. The US Department of Health and Human Services (DHHS) and the USDA released the 2020-2025 dietary guidelines for Americans, which identified nutrients consumed below the estimated average requirements. Nearly 30% of men and 60% of women over 19 years old do not consume enough calcium, and more than 90% do not consume enough vitamin D [21]. Other nutrients of top concern were potassium, fiber, and choline.
General Recommendations:
Eat more colorful vegetables, fruits, dairy, whole grains, and seafood.
Consume less refined grains, added sugars, saturated fat, and sodium.
Men aged 19-31: diversify your intake and eat less meat.
Women on a 2,000-calorie diet: eat more red and orange and starchy vegetables (since they’re getting, on average, enough dark leafy greens), 5.5 ounces of protein a day, mostly from meat, poultry, and eggs; 27 grams of oil, and a 240-calorie allowance for outside foods.
Consume healthy fats and enough protein, but maintain moderation.
Don't overly restrict; you can enjoy a treat now and then.
Healing the Gut: What to Avoid – Lectins, Gluten, and More
To protect gut barrier integrity, avoid processed foods, which contain preservatives, stabilizers, fillers, and thickeners, such as guar gum, xantham gum, and polysorbate-80. These types of ingredients can sneak their way into purportedly “healthier” products, such as multivitamins and nutraceuticals, and can sound deceptively innocent, such as carboxymethylcellulose (CMC). Be sure to carefully read ingredients before buying. In addition, avoid a high fat diet [54, 55], canola oil and other highly processed oils, excess artificial or natural sugars (including fructose), high-glycemic foods [13, 56], GMO foods, and excess salt [57].
For those with trouble digesting gluten, including people with Celiac disease, gluten intolerance, or non-Celiac gluten sensitivity (NCGS), avoiding wheat products and gluten is also beneficial. Gliadin, a component of gluten, interacts with the immune system, causing tight junction reorganization and leaky gut [58].
[Note: since gluten-containing foods such as breads and cereals are often enriched with vitamins and minerals, eliminating gluten products from one’s diet can cause major changes in one’s nutrient status. Consult with your healthcare provider, such as a doctor or nutritionist, to ensure you have a plan to replace these nutrients, whether through dietary sources, herbs, supplements, botanicals, or nutraceuticals.]
Gluten is part of a larger class of antinutrients called lectins, which can cause bloating and leaky gut [59]. For most lectin-containing foods, cooking for 5-10 minutes, particularly with wet heat (pressure cooking or boiling), reduces lectin content down to nothing. However, nuts (e.g. cashews), seeds, tomatoes, bell peppers, and A1 cow milk may be consumed raw, so these are the biggest sources of lectins.
Some GMOs have passed under the radar because they harness naturally-occurring processes, but that doesn’t mean they don’t come without dangers. GMO foods can also compromise the gut barrier. Bacillus thuringiensis (BT) is a bacteria that expresses an endotoxin as a natural defense mechanism. This process has been harnessed as an insecticide in crops, and some corn is genetically modified to express this endotoxin. BT toxins from insecticide use can poke holes in insects’ intestinal cell walls, causing leaky gut; BT endotoxin also pokes holes in human cells [60]. Avoid BT-treated corn and potatoes.
Some of these GMOs are highly insidious and may seem “natural” at first glance, since they can make use of naturally-occurring processes in particular species. More about the dangers of certain genetic modifications (GMO foods) is included in the full report.
Gut Health: What to Add
Buy organic. Proper nutrition helps intestinal epithelial cells function. For optimal gut barrier integrity, ensure you are intaking adequate levels of vitamin A [61-63], vitamin D [63-65], zinc [66], fiber [67], aryl hydrocarbon receptor agonists such as tryptophan, curcumin, quercetin, and gallic acid [68], L-glutamine [69], and polyphenols such as anthocyanins [69].
See more about the recommendations, benefits, and risks of various nutrients such as vitamin A, omega-3s, choline, L-glutamine, and soy isoflavones in the full report.
Urbanization and Excess Hygiene
Exposure to microbes early in life is critical for immune system development. Having a relationship with land allows a healthy immune tolerance to develop, while an excessively sterile environment leaves barren, inviting terrain for autoimmune disease and allergies. Indeed, the rise in autoimmune diseases is attributed in part to excess hygiene. Urbanization and industrialization were implicated in reducing the mucosa barrier and contributing to numerous diseases, as reported by Akdis in a 2021 Nature Reviews Immunology paper [29].
Toxic Chemicals
The combination of synthetic compounds and a sanitary lifestyle spent indoors is creating fewer co-evolved microbial relationships and disrupting immune homeostasis.
Industrial chemicals, including pesticides [39] like glyphosate [40-42], microplastics [43], dishwasher detergents [44], household cleaning products, sodium lauryl sulfate (SLS) [45], persistent organic pollutants, food contaminants, and air pollution can be added to the list of epithelial barrier-damaging agents we’re chronically exposed to, and they are all correlated with leaky gut.
Below are practical tips to minimize barrier-disrupting industrial chemicals:
To avoid ingesting plastics, steep unbleached paper tea bags (or free, loose-leaf tea), never microwave food in plastic containers, avoid using plastic cutting boards, make swaps for floss and menstrual products, and wear natural fabrics.
For household cleaners, opt for gentle detergents and rinse aids, and opt for sulfate-free shampoos.
Buy organic, especially wheat, grains, soybeans, wine, and produce on the dirty dozen list. Glyphosate has been detected in breastmilk, so be especially cautious if pregnant or breastfeeding.
It’s worth noting some foods naturally contain high levels of toxic chemicals, for example, tuna and rice (heavy metals), farmed salmon (plasticizers), cassava (cyanide-releasing compounds, if not properly prepared), processed meats (nitrates), and fried foods (e.g. potato chips and fries – carcinogenic acrylamides).
For a more detailed discussion on the role of pesticides (e.g. atrazine, organophosphorus, and chlorpyrifos), plastics (including BPA, styrofoam, bioplastics), rinse aids, and PoPs in gut health, see the full-length guide.
Alcohol, Cigarettes, Opiates, and Other Psychoactive Substances
Alcohol is known to cause intestinal permeability and can also cause hormone and neurotransmitter imbalance and contribute to the risk of breast cancer [8]. The ethanol metabolite acetaldehyde also contributes to leaky gut [46].
Chronic alcohol use disorder has been shown to lead to intestinal permeability via microbiota dysbiosis. Not all chronic alcohol misuse leads to leaky gut; it appears that both microbiota dysbiosis and alcohol misuse are necessary to induce intestinal permeability. Within two weeks of abstaining from alcohol, intestinal permeability is restored, but microbiota dysbiosis may persist. This also shows that microbiota dysbiosis can exist without leaky gut [47].
Morphine and fentanyl have also been shown to impair intestinal barrier function [48].
Cigarette smoke and e-cigarettes have also been shown to compromise the intestinal barrier [49, 50]. Smoking also causes gut dysbiosis.
According to current literature, cannabis does not impair intestinal permeability; however, more research is needed on effects of cannabis smoking on the epithelial barrier. Additionally, there is no peer-reviewed evidence that psilocybin impairs intestinal permeability. There is also not enough evidence to conclude whether stimulants such as caffeine, cocaine, or amphetamines cause leaky gut [51].
Infection, toxins in food, and microbial endotoxins
Toxins in food and water can contribute to allergy development. A 2022 paper published in Frontiers in Allergy showed that co-exposure to toxins from microbes and food allergens sensitizes the immune system to developing food allergies by damaging the epithelial barrier. That is, mycotoxin and cholera toxin had an adjuvant effect in the development of peanut allergies [52]. Aflatoxin, a common food toxin, is found in moldy grains and nuts (peanuts, corn, and wheat).
Specific enteropathogens can harm gut health, including bacteria and eukaryotes (fungi, protozoa, and parasites). Bacteroides fragilis [46, 53, 54], Clostridium difficile [55], Staphylococcus aureus, certain E. coli strains [46, 56, 57], certain bacteria involved in food poisoning (Salmonella and Listeria) and others have been linked to leaky gut. Various fungi (particularly Candida) and parasites like Toxoplasma gondii [54] can wear down the gut lining and open tight junctions. More recent investigations are also revealing a role for bacteriophages, the viruses that infect bacteria, in intestinal permeability. (See our full report for a comprehensive guide and more species- and strain-specific information).
Medications
Certain medications and over-the-counter drugs carry risk of GI-related side effects.
Medications, including antibiotics, the hormonal contraceptive pill [58] as well as non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of IBD [59-61].
Contraceptives
A meta-analysis of case-controlled and cohort studies revealed that individuals exposed to oral contraceptives had a 24% and 30% increased risk for developing Crohn’s disease and ulcerative colitis, respectively, compared with those not exposed to the medication [62]. Meanwhile, normally menstruating women did not have different intestinal permeability than men [63].
Antibiotics
Certain antibiotics, such as neomycin and bacitracin [64] may improve intestinal integrity, while others such as metronidazole [65] may weaken the mucosal barrier. Thus, the effect of the antibiotic on the gut depends on identity, dosage, and how it’s combined. Further distinctions about the effect of different types of antibiotics are available in the free full report).
NSAIDs
In 2001, GlaxoSmithKline demonstrated that indomethacin, flurbiprofen, or diclofenac increased the vascular leakage of radiolabeled albumin in the jejenum, determined 24 hours later [66]. A meta-analysis published in the Journal of Gastroenterology in 2009 showed that NSAIDs increased intestinal permeability [67]. Chronic use is likely more harmful than sporadic, occasional use when medically needed.
Other Drugs
Steroids, acid blockers, hormonal replacement, antipsychotic medications, and opioids all damage the gut and cause microbiome problems and are detrimental to gut barrier function [68]. Always prioritize dietary modifications as a health buffer, but take medications when they are medically necessary.
Certain chemotherapy drugs may cause intestinal barrier injury [6, 69]. Preclinical data also suggests that proton pump inhibitors increase tight junction barrier permeability [70] and damage mitochondria. Alcohol and corticosteroid (e.g. hydrocortisone) exposure may act through glucocorticoid receptors in the intestinal epithelial cells, and they have been shown to increase gut permeability [71].
Recognizing certain lifesaving medications are medically necessary, an appropriate action is to mitigate the damage through epithelial-restoring foods. However, it is recommended to work with a specialized nutritionist qualified to provide recommendations in the context of certain disease diagnoses, such as cancer.
Ionizing Radiation
Ionizing radiation causes intestinal injury and microbial translocation [72-78], but certain nutraceuticals demonstrate radioprotective properties, mitigating damage [79-89]. (Learn more about sources of ionizing radiation and specific nutraceuticals in the full report).
Key takeaways: Causes of Leaky Gut
Modifiable Factors: Some factors, like aging, genetics, and oxidative stress, are out of our control. Other factors, like stress, depression, sleep, exercise, diet, and drug use, are in our control.
Play in the dirt. A relationship with the land cultivates a robust, diverse microbiome and a tolerogenic immune system.
Go green and clean. To the extent possible, minimize plastic use, choose household cleaners with more natural ingredients, buy organic, and get fresh air. If you live in a city, collect plants, use an air purifier and humidifier, and make it a point to escape the city once in awhile.
Supplement. Take multivitamins and minerals.
Eat more whole foods and vegetables, enough fiber, choline, tryptophan- and L-glutamine-rich protein, omega-3 fats, as well as antioxidants like quercetin, gallic acid, and anthocyanins.
Read ingredients labels on everything before you buy! Eat less processed food, refined grains, and added sugars.
Consult with an allergist if you suspect you may have a food allergy.
If you’re interested in learning more about the causes of leaky gut, I have put together a free comprehensive report on this topic.
Thank you for reading. If you found this article valuable, feel free to share it, hit the heart button, or leave a comment.
This article is part 4 of a larger 5-part series on leaky gut:
Causes of leaky gut
Solutions to leaky gut
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