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Published on August 29, 2025

“Irritable gut,” often referred to as “leaky gut,” describes a state of heightened permeability within the mucosal lining of the small intestine. It’s a disruption of the finely tuned barrier function that governs what passes between the gut and the bloodstream. While the intestinal lining has a natural, regulated semi-permeability to absorb nutrients, this balance can be disturbed.

Under healthy conditions, tight junctions—protein complexes that act as gatekeepers between cells—meticulously control what enters circulation. When these junctions become dysfunctional, the intestinal barrier’s integrity is compromised, allowing for the uncontrolled passage of substances like bacteria, toxins, and undigested food particles into the bloodstream.

Understanding the Gut Barrier

The intestinal lining is a single layer of epithelial cells held together by tight junctions. This barrier selectively allows nutrients to pass while preventing harmful substances from entering the bloodstream. When these junctions become loose or damaged, the gut becomes “irritable.”

Lipopolysaccharides (LPS): The Inflammatory Culprit

A key player in the irritable gut scenario is lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria. In a healthy gut, LPS is contained. However, in an irritable gut, LPS can cross the compromised barrier and enter the bloodstream. LPS is a potent pro-inflammatory molecule that triggers an immune response, leading to systemic inflammation. This inflammation can contribute to a wide range of health problems, including:

Autoimmune diseases: such as widespread pain and joint pain.
Food sensitivities and allergies.
Inflammatory gut issues.
Skin conditions like eczema and psoriasis.
Mood disorders: such as depressive states and anxious thoughts.
Metabolic issues: like insulin resistance and obesity.
Brain fog and cognitive decline.

Factors Contributing to Irritable Gut

Several factors can contribute to increased intestinal permeability:

Diet: A diet high in processed foods, sugar, and refined carbohydrates can damage the gut lining.
Stress: Chronic stress can disrupt the gut microbiome and weaken the gut barrier. Irritable gut is very frequent with trauma patients in my clinic.
Medications: Certain medications, such as NSAIDs and antibiotics, can damage the gut lining.
Infections: Bacterial overgrowth (SIBO), yeast overgrowth (Candida), and parasitic infections can contribute.
Dysbiosis: An imbalance in the gut microbiome, with an overgrowth of unhelpful bacteria, can damage the gut lining.
Alcohol: Excessive alcohol consumption can irritate and damage the gut lining.

How to Test for Irritable Gut

Differential Sugar Test: Considered the most reliable option. It involves drinking a sugary beverage and measuring these sugars in the urine six hours later. High levels of lactulose indicate hyperpermeability.
Serum Zonulin: Not as accurate as the differential sugar test, as serum zonulin levels are highly variable.
Antibody Markers: Zonulin, LPS, occludin, and actomysin antibodies are more reliable than serum zonulin.
Intestinal Biopsy: While accurate, it’s too invasive and expensive for routine use.

Solutions to Address Irritable Gut

A holistic approach focuses on identifying and addressing the root causes. This approach typically involves:

Comprehensive Assessment: A detailed medical history and testing to assess gut permeability, microbiome composition, and inflammatory markers.
Personalized Therapy:
- Remove: Identify and remove triggers like food sensitivities, pathogens, and toxins.
- Replace: Replace digestive enzymes and hydrochloric acid if deficient.
- Reinoculate: Restore beneficial gut bacteria with probiotics and prebiotics.
- Repair: Support gut lining repair with nutrients like L-glutamine, zinc, and omega-3 fatty acids.
- Rebalance: Address lifestyle factors like stress management and sleep.
Dietary Modifications: An elimination diet to identify and remove food sensitivities. Focus on a nutrient-dense diet rich in whole foods, fiber, and healthy fats while limiting or avoiding processed foods, sugar, and alcohol.
Supplementation: Probiotics and prebiotics to restore gut microbiome balance, L-glutamine to support gut lining repair, zinc to support tight junction integrity, and omega-3 fatty acids to reduce inflammation.
Stress Management: Using practices such as meditation, yoga, and deep breathing exercises.
Addressing Underlying Infections: Therapy for SIBO, Candida, or parasitic infections, if present.

The Importance of Gut Health

A healthy gut is essential for overall wellness. By addressing intestinal permeability and restoring gut health, functional medicine aims to improve not only digestive symptoms but also a wide range of other health symptoms.

Start a gut health journal to track your daily food intake and symptoms.

Medical Disclaimer: This article has been written by a licensed health professional and is intended for general informational purposes only. It does not substitute for personalised medical advice, diagnosis, or treatment. Readers should always seek the guidance of a qualified healthcare provider with any questions regarding a medical condition or health objectives. Never ignore or delay seeking medical advice based on information presented here.

References

Lacy BE, Wise JL, Cangemi DJ. Leaky gut syndrome: Myths and management. Gastroenterol Hepatol (N Y). 2024;20: 264–272.
Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017;8: 598.
Wang J, He Y, Liu Z, Liu X, Jing Y. Glutamine peptides: Preparation, analysis, applications, and their role in intestinal barrier protection. Nutrients. 2025;17: 1017.
Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012;10: 1096–1100.
Vanuytsel T, Tack J, Farre R. The role of intestinal permeability in gastrointestinal disorders and current methods of evaluation. Front Nutr. 2021;8: 717925.

Last Updated on August 29, 2025

Leaky Gut: Understanding Intestinal Permeability