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.
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
- Chronic stress
- Toxins
- A poor diet
- Infections
- Medications such as NSAIDs and antibiotics
- Bacterial imbalances
- Alcohol
- Pancreatic insufficiency
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
- Ongoing bloating, gas, diarrhea or constipation
- Food reactions that seem to be multiplying
- Fatigue, skin flares or joint aches alongside gut symptoms
- 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.
Want help finding the root of your gut symptoms?
A free 15-minute consultation with Dr. Kneessi. No cost, no obligation. In-office in Odenton, MD or by telehealth.
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?
Chronic 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
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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