Your gut microbiome is made up of trillions of microbes that influence digestion, metabolism, mood and immunity. A large proportion of the body’s immune tissue sits in and around the gut wall, which is why gut health and immune function are so closely linked.

Research suggests that increased intestinal permeability, often called “leaky gut”, may play a role in how some autoimmune conditions develop and progress.

The link between the gut and conditions like coeliac disease, Crohn’s disease and ulcerative colitis is easy to see. The connection to autoimmune conditions elsewhere in the body, such as type 1 diabetes, multiple sclerosis or rheumatoid arthritis, can be harder to picture.

So, let’s break it down.

What is the gut? Your digestive system and gut microbiome explained

“Gut” is another word for your gastrointestinal tract, or digestive system. Digestion begins in the mouth and continues in the stomach, but most food is broken down and absorbed in the small intestine. The large intestine absorbs water and electrolytes, and it is where gut bacteria ferment fibre into beneficial compounds called short-chain fatty acids. Waste is then expelled via the rectum.

The inner lining of the gut forms the intestinal barrier. It has several layers working together: a protective mucus layer, a single layer of cells joined by “tight junctions”, and immune cells sitting just beneath. The barrier is semipermeable. It lets nutrients, water and electrolytes through while keeping bacteria, toxins and other unwanted substances inside the gut to be excreted.

What is leaky gut? How intestinal permeability develops

The tight junctions between gut cells open and close in a regulated way. When the barrier is disrupted, these junctions loosen and the mucus layer can thin. This allows more to pass between the cells than should. This is known as increased intestinal permeability, or leaky gut. It can occur in both the small and large intestine.

What crosses is mostly bacterial products, such as lipopolysaccharide (LPS) from bacterial cell walls, along with toxins and fragments of food proteins. Immune cells beneath the lining recognise these as potential threats and respond, which creates inflammation.

Short-term, this is a normal protective response. However, when barrier disruption is ongoing, low-grade inflammation can persist and may contribute to wider health issues, including autoimmune disease.

What causes leaky gut? The main triggers that disrupt the intestinal barrier

1. Gluten. Gliadin, a protein found in gluten, can trigger the release of zonulin, a protein that temporarily loosens the tight junctions between gut cells. This response is strongest and most persistent in people with coeliac disease. Research suggests a smaller, short-lived effect may also occur in people without coeliac disease, including those with non-coeliac wheat sensitivity.
2. Dysbiosis. The gut microbiome plays a key role in keeping the barrier intact. Beneficial bacteria produce short-chain fatty acids such as butyrate, which fuel the cells of the gut lining and support tight junction integrity. When the microbiome is out of balance, these protective functions decline. A low-fibre diet can also shift bacteria towards feeding on the protective mucus layer, thinning the gut’s first line of defence. Bacterial overgrowth in the small intestine (SIBO) is another known trigger for zonulin release.
3. Elevated blood sugar. Persistently high blood glucose can reprogram the cells of the gut lining, weakening the junctions between them and allowing microbial products into circulation. In humans, poorer long-term glucose control (HbA1c) has been linked to greater leakage of microbial products. Diets high in sugar and fructose may also affect the barrier indirectly by altering the gut microbiome.
4. Stress. Psychological stress can increase gut permeability directly. Stress hormones such as corticotropin-releasing hormone (CRH) activate immune cells called mast cells in the gut wall, which loosens the barrier. Stress can also alter the gut microbiome over time. The effect appears to vary between individuals, and human research is still developing.
5. Alcohol. Alcohol and its by-product acetaldehyde directly disrupt the tight junctions between gut cells. Regular or heavy intake also promotes dysbiosis and bacterial overgrowth, which further weaken the barrier.
6. NSAIDs. Non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, diclofenac and aspirin are among the best-documented causes of increased gut permeability. They reduce protective prostaglandins in the gut lining and directly damage the energy-producing mitochondria in gut cells. Permeability can rise within hours of a single dose, and regular use commonly causes inflammation and injury in the small intestine

Leaky gut and autoimmune disease: how are they connected?

Autoimmune disease develops when the immune system loses “tolerance”, its ability to tell the body’s own tissues apart from genuine threats. Researchers think three factors often come together: a genetic predisposition, an environmental trigger, and a gut barrier that lets more through than it should.

When bacterial products and food proteins cross a disrupted barrier, the immune system is repeatedly activated. In someone who is genetically susceptible, this ongoing activation and inflammation may help tip the immune system towards attacking the body’s own tissues.

The outcome depends on the condition. In coeliac disease, gluten drives an immune response that damages the small intestine. In other autoimmune conditions, the immune response targets joints, the thyroid, the pancreas or the nervous system.

This model is well supported in coeliac disease. For many other autoimmune conditions, increased permeability is a likely contributor rather than a proven cause, and research is ongoing.

Can leaky gut improve? How gut microbiome testing helps

The gut lining renews itself every few days, so barrier function can improve when the factors disrupting it are addressed. For many people with autoimmune conditions, supporting gut health can help reduce inflammation, ease symptoms and improve quality of life, alongside their medical care.

Microbiome stool testing shows us what is actually happening in your gut: which bacteria are overgrown, which beneficial species are missing, and how that may connect to your symptoms. SIBO breath testing and a review of your pathology can add to the picture. From there, we build a targeted plan rather than guessing.

That plan may include microbiome-focused nutrition and supplements, stress and lifestyle support, and, where appropriate, a structured elimination and reintroduction approach such as the Autoimmune Protocol (AIP). Small studies of AIP in inflammatory bowel disease and Hashimoto’s thyroiditis have reported improvements in symptoms and quality of life.

5 natural ways to support leaky gut healing

1. Anti-inflammatory foods. Inflammation is a key driver of both leaky gut and autoimmune disease. Colourful fruit and vegetables, herbs and spices such as turmeric, and omega-3-rich oily fish (salmon, sardines, mackerel, anchovies, herring) all help. Plant foods contain polyphenols, which have anti-inflammatory properties and also feed beneficial gut bacteria.
2. Fermented foods. Fermented foods such as yoghurt, kefir, sauerkraut, kimchi and kombucha introduce live microbes and beneficial compounds. In one study, a diet high in fermented foods increased microbiome diversity and reduced markers of inflammation.
3. Prebiotic fibre. Prebiotics are fibres that feed beneficial bacteria, helping them produce barrier-supporting short-chain fatty acids. Good sources include onion, garlic, leek, asparagus, artichoke and green bananas. Many of these foods are high-FODMAP, so if you have IBS or SIBO, introduce them slowly or with guidance. Targeted prebiotic supplements can help if a high-fibre diet causes discomfort.
4. Glutamine. Glutamine is an amino acid that fuels the cells of the gut lining and supports tight junction integrity. In a clinical trial in people with post-infectious IBS, glutamine supplementation reduced symptoms and improved gut permeability. Food sources include meat, fish, eggs, dairy, tofu and legumes.
5. Reduce stress. Because stress directly affects the gut barrier, calming the nervous system is part of gut healing. Daily practices such as meditation, slow breathing or mindfulness can reduce stress, support sleep and help regulate immune function.

Gut health support for autoimmune conditions

If you’re living with an autoimmune condition or ongoing gut symptoms and want to understand what’s driving them, book a consultation. Together we’ll look at your gut microbiome, history and symptoms, and build a plan based on what your gut actually needs.

This article is general educational information and is not a substitute for individual medical advice. Please continue working with your GP or specialist for the management of any autoimmune condition.

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