Quick answer: Leaky gut is rarely caused by one trigger. It usually builds over time from a mix of factors such as chronic stress, a poor diet, infections, certain medications, alcohol, toxins and microbial imbalance. Underneath these triggers are three main drivers that weaken the gut lining: chronic inflammation, oxidative stress and dysbiosis.
Key takeaways
Leaky gut rarely has a single cause and usually builds from several factors over time.
Common triggers include chronic stress, everyday exposures, a poor diet, infections and medications such as NSAIDs and antibiotics.
These triggers tend to weaken the tight junctions that seal the gut lining, which can let inflammatory signals reach the bloodstream.
Rarely one trigger
It’s rarely a single trigger that causes leaky gut. It’s an accumulation of factors over time that can lead to an inflammatory reaction and a weaker gut barrier. Increased intestinal permeability (“leaky gut”) is an active area of research. It is not a formal diagnosis in conventional medicine, and much of the evidence comes from lab and early human studies. New to the topic? Start with the introduction to leaky gut.
The most common triggers
The most common triggers are chronic stress, toxins, a poor diet and infections, along with medications such as NSAIDs and antibiotics. Bacterial imbalances, heavy alcohol use and pancreatic insufficiency can also play a part.
The root drivers
Three processes tie these triggers together by weakening the tight junctions that seal the gut lining.
Chronic inflammation
Ongoing inflammation increases inflammatory messengers (cytokines) that loosen tight junctions. Learn more in chronic inflammation and the gut.
Oxidative stress
When reactive oxygen species outpace your antioxidant defenses, they can damage the proteins that hold gut cells together.
Dysbiosis
Dysbiosis is an imbalance in the gut’s microbial community. It can reduce tight junction proteins and increase lipopolysaccharides (LPS), inflammatory toxins from certain bacteria. See microbial diversity and dysbiosis.
Why this matters for healthy aging
A weakened gut barrier lets inflammatory signals reach the bloodstream, adding to the low-grade, body-wide inflammation that accelerates aging. Microbial balance also tends to decline with age, which makes gut care a long-term investment.
What you can do
- Look at your own triggers: stress, diet, alcohol and medications (see dietary factors and infections and drugs)
- Never stop a prescribed medication without talking to your doctor
- Follow a structured plan (see the multi-mechanism approach)
When to see a naturopathic doctor
It may be time to see a naturopathic doctor if you have ongoing bloating, gas, diarrhea or constipation, or food reactions that seem to be multiplying. The same is true if you have fatigue, skin flares or joint aches alongside gut symptoms, or if you want a personalized gut plan instead of guessing.
See a medical provider promptly for blood in your stool, black stools, unexplained weight loss, persistent vomiting, severe abdominal pain, fever, or trouble swallowing.
What the research shows
Hard exercise can briefly loosen the gut barrier. In a 1997 study by Pals and colleagues, 6 healthy, fit volunteers rested or ran on a treadmill for 60 minutes at 40%, 60% or 80% of their maximum effort. Only the hardest run raised small intestine permeability, to about twice the resting level, and it did not cause more digestive symptoms. With only six people and a single session, this shows a short-term effect of intense exercise, not a lasting problem.
Alcohol is another well-studied trigger. In a 1999 study by Keshavarzian and colleagues, people with alcohol use disorder and liver disease had a much higher urinary lactulose-to-mannitol ratio than healthy controls (0.703 versus 0.019), while people with alcohol use disorder but no liver disease, and people with liver disease from other causes, had normal intestinal permeability. The abstract does not report group sizes, and this kind of study cannot prove that leaky gut came first.
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Questions to bring to your clinician
These questions can help you get the most out of your next visit.
Which of these triggers are most relevant to my history?
Which leaky gut triggers might apply most to me?
Which trigger would be most worth reducing first?
How would we know whether removing triggers is helping?
Frequently asked questions
What is the main cause of leaky gut?
Usually a combination of triggers, rather than one cause.
Can stress cause leaky gut?
Stress is one of the factors linked to a weaker gut barrier.
Do NSAIDs affect the gut lining?
Yes. Regular NSAID use can irritate and damage the gut lining.
Is leaky gut a recognized diagnosis?
Increased intestinal permeability is studied, but “leaky gut syndrome” is not a formal diagnosis.
Sources
- Pals KL, Chang RT, Ryan AJ, et al. Effect of running intensity on intestinal permeability. J Appl Physiol (1985) 1997. PMID: 9049739. https://pubmed.ncbi.nlm.nih.gov/9049739/
- Keshavarzian A, Holmes EW, Patel M, et al. Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage. Am J Gastroenterol 1999. PMID: 9934756. https://pubmed.ncbi.nlm.nih.gov/9934756/
- Bjarnason I, et al. Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs. Gastroenterology 2018. PMID: 29221664. https://pubmed.ncbi.nlm.nih.gov/29221664/
- Bishehsari F, et al. Alcohol and Gut-Derived Inflammation. Alcohol Res 2017. PMID: 28988571. https://pmc.ncbi.nlm.nih.gov/articles/PMC5513683/
- Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta 2009. PMID: 18952050. https://pmc.ncbi.nlm.nih.gov/articles/PMC2699410/
- Rao R. Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Front Biosci 2008. PMID: 18508729. https://pmc.ncbi.nlm.nih.gov/articles/PMC6261932/
- Vanuytsel T, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014. PMID: 24153250. https://pubmed.ncbi.nlm.nih.gov/24153250/
- MedlinePlus: Digestive Diseases
This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before starting supplements or changing medications, especially if you are pregnant, nursing, or managing a health condition.
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