By: Kim Ross, DCN, CNS, LDN, IFMCP

1. Introduction
2. A Healthy Barrier and Its Functions
3. A Compromised Barrier
4. Factors that Impact GI Integrity and Lead to a Self-Tissue Response
5. Nutrition, Lifestyle and Health Components
6. Nutrient Solutions to Build the Intestinal Barrier
7. Pure Encapsulations Nutrient Solutions
8. Conclusion
9. Resources

Introduction

The intestinal barrier is more than just a digestive checkpoint - it's a key defender against non-beneficial microorganisms, toxins, and antigens while allowing the body to absorb vital nutrients. When this barrier is compromised, it can lead to a cascade of symptoms, including occasional bloating, abdominal discomfort, irregular bowel movements, and nutrient malabsorption.

One common consequence of a weakened barrier includes intestinal concerns, often triggered by self-tissue response. According to the CDC, over 3.1 million Americans experience intestinal immune concerns,¹ which can disrupt nutrient absorption and weaken overall immunity.

This article will explore the essential nutrients that support the mucosal immune system and strengthen the intestinal barrier, offering insights into how dietary interventions can help maintain gut integrity and overall health.

A Healthy Barrier and Its Functions

The intestinal barrier consists of a monolayer of specialized epithelial cells that line the gut lumen, forming a selectively permeable barrier. These epithelial cells are sealed together by tight junction proteins, including occludin, claudin-1, and zonula occludens-1 (ZO-1).^2,3 Tight junctions function as "gatekeepers," determining what substances can pass through the intestinal lining into the bloodstream while preventing the entry of harmful microorganisms, toxins, and antigens.

The intestinal barrier also includes a mucus layer, which provides physical protection by preventing direct contact between microbes and the epithelial cells. It contains antimicrobial peptides and secretory immunoglobulin A (sIgA), which neutralize non-beneficial microorganisms and contribute to immune defense. This layer is rich in immune cells such as macrophages, dendritic cells, and T-cells, which play key roles in maintaining immune homeostasis.³

The primary functions of the gut barrier include:⁴

• absorption of nutrients
• regulation of immune responses
• maintenance of intestinal homeostasis
• prevention of the translocation of harmful substances
• supporting bidirectional communication between the gut microbiota and the immune system

A Compromised Barrier

When the integrity of the gut barrier is compromised, it can lead to increased intestinal permeability, commonly called "leaky gut." Increased permeability allows larger molecules, such as undigested food particles, toxins, and microbes, to enter the bloodstream, potentially triggering an unbalanced state and immune activation. This, in turn, can lead to persistent intestinal distress and self-tissue response in the intestines, further exacerbating symptoms and contributing to systemic changes.

Factors That Impact GI Integrity and Lead to a Self-Tissue Response

The integrity of the intestinal barrier and the development of a self-tissue response in the intestines is rarely a result of one factor. Instead, it is a multifactorial process influenced by numerous factors, including the health of the microbiome, immune and cytokine responses, and nutrition, lifestyle, and health components.

The Health of the Microbiome

The gut microbiome is a complex ecosystem of nearly 100 trillion microorganisms that maintain mucosal health.² Beneficial microbes such as Bifidobacteria, Lactobacilli, enterococcus, and Clostridium produce short-chain fatty acids (SCFAs), which support tight junction integrity and signaling.²

Conversely, a microbial imbalance resulting from low microbial diversity or gastrointestinal infections can increase intestinal permeability and promote an increased immune response. Evidence suggests that individuals with a self-tissue response in the intestines have a reduction of beneficial bacterial species in the gastrointestinal tract.⁵

The Immune and Cytokine Responses in the Gut

The gut-associated lymphoid tissue (GALT) is an integral part of the immune system, responsible for responding to non-beneficial bacteria while maintaining tolerance to dietary antigens and commensal bacteria. Cytokines such as interleukin-10 (IL-10) promote immune tolerance, whereas excessive production of cytokines like IL-6 and TNF-α disrupt mucosal balance. Activation of these cytokines can perpetuate barrier and tissue changes, contributing to systemic immune activation.^6,7

Nutrition, Lifestyle & Health Components

Nutrition: The Standard American Diet (Western Diet) contains a high intake of refined sugars, processed carbohydrates, red or processed meat, omega-6 fatty acids, and alcohol, exacerbating the body's cytokine balance processes. The way of eating is also partially responsible for decreased bacterial diversity in the gut and contributes to inadequate intake of essential vitamins and minerals. Poor nutrient absorption is a common presentation for people with a self-tissue response in the intestines.^8,9

Conversely, a diet rich in fruits and vegetables, fiber, omega-3 fatty acids, fish, grains, and legumes protects and supports a healthy GI barrier. Studies have shown that eliminating some food groups, such as gluten and dairy or other known food allergies or intolerances, may help reduce GI symptoms and support a self-tissue response.⁹ Special attention should be given to replacing vitamins and minerals, such as B vitamins, vitamin D, electrolytes, and omega-3 fatty acids, as indicated.¹⁰

Lifestyle: Perceived stress that is uncontrolled or not well managed is considered a predictor of the exacerbation of GI symptoms and self-tissue response.¹¹ Poor sleep quality is associated with elevated levels of IL-6, TNF-α, nuclear factor-kB (NF-kB), and CRP (C-reactive protein), known markers of the immune system.¹²

Health Components: General health components such as a history of intake of medications, exposure to environmental toxins and genetic predisposition also play a role in the susceptibility to a compromised intestinal barrier and immune response.

Nutrient Solutions to Build the Intestinal Barrier

Glutamine is the most abundant amino acid in the body. It is the primary energy source for enterocytes (the cells that line the small intestine and colon), utilizing about 30% of total glutamine.^13,14 It also helps maintain healthy intestinal integrity by enhancing the intestine's protective mucosal lining and promotes tissue repair from metabolic stress.^14‡

Studies have demonstrated that L-glutamine supplementation reduces intestinal permeability and supports outcomes in patients with compromised barrier integrity.^13‡

Arabinogalactan, a fiber derived from larch trees, is a prebiotic that promotes the growth of beneficial gut bacteria. such as Bacteroidetes, Bifidobacterium, and Faecalibacterium praisnitzii, which are crucial for proper gut-associated lymphoid tissue (GALT) function and development.¹⁵ These bacteria produce SCFAs, including butyrate, which enhance epithelial integrity and modulate cytokine production.^‡

Arabinogalactan also has immunomodulatory properties, supporting the production of natural killer (NK) cells and promoting mucosal immunity.¹⁶ It may also promote healthy production of cytokines, which mediate cell-to-cell communication between cells involved in the immune response. Its dual role as a prebiotic and immune supporter makes it a valuable addition to protocols to restore gut health.^‡

Perilla (Perilla frutescens) is a traditional herb rich in polyphenols and rosmarinic acid. which promote cytokine balance and antioxidant effects. Its active compounds reduce the production of cytokines such as IL-6 and TNF-α, which are implicated in intestinal immune changes.^17‡

In a randomized, controlled trial involving 50 individuals, 150 mg of Benegut^® Perilla frutescens extract twice daily offered significant support for GI comfort.¹⁸ Perilla also stabilizes mast cells, reducing hypersensitivity reactions that can contribute to mucosal damage.^19‡

Additionally, its antioxidant properties help neutralize reactive oxygen species (ROS), protecting the intestinal lining from oxidative stress.²⁰

Astragalus (Astragalus membranaceus) is a well-known adaptogenic herb with a long history of use in Traditional Chinese Medicine (TCM). It promotes immunity by supporting B and T lymphocyte production, balancing Th1/Th2, and modulating cytokine response.²¹ It also protects the intestinal barrier by upregulating tight junction proteins and secretory IgA (sIgA) production. This key immune component coats the intestinal lining and prevents the adherence of non-beneficial microorganisms.²² Its adaptogenic properties further support resilience against stress, a contributing factor to a compromised intestinal barrier.^23‡

Deglycyrrhizinated licorice (DGL) supports the healing of the GI barrier and other mucous membranes by increasing blood supply to mucosa, increasing the production of mucus, which acts as a protective barrier for the intestinal lining and improves the life span of intestinal cells.^24‡

Pure Encapsulations^® Nutrient Solutions

Pure Encapsulations offers expertly crafted supplements made with high-quality, pure ingredients and supported by verifiable scientific research. These products are designed to complement personalized care plans.^‡

Epi-Integrity powder: is a carefully formulated blend of glutamine, prebiotic fiber, and herbal extracts that support the modulation of mucosal immune responses and promote gastrointestinal (G.I.) barrier integrity. It helps maintain a balanced microbiome, provides mucosal protection, and supports epithelial cell health for optimal gut function.^‡

Suggested Use: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice. Shake or stir until dissolved.

Conclusion

Restoring intestinal barrier integrity and supporting mucosal immune responses are essential for addressing symptoms associated with self-tissue responses in the gut. Healthcare providers can leverage evidence-based nutritional strategies to address the underlying factors contributing to a compromised barrier. Nutrients such as L-glutamine, arabinogalactan, perilla, Astragalus, and DGL offer targeted support for mucosal repair, cytokine modulation and immune balance.^‡

Resources

Gastrointestinal Self-Tissue Response Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient's intestinal health.^‡

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

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