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Barrier Builders: Nutrients to Support Mucosal Immune Responses and the Intestinal Barrier

  • Feb 28, 2025
Pure Encapsulations Pro Blog
Learn how nutrients, the microbiome, and lifestyle choices impact mucosal immunity and support a resilient intestinal barrier.Learn how nutrients, the microbiome, and lifestyle choices impact mucosal immunity and support a resilient intestinal barrier.
Learn how nutrients, the microbiome, and lifestyle choices impact mucosal immunity and support a resilient intestinal barrier.

Barrier Builders: Nutrients to Support Mucosal Immune Responses and the Intestinal Barrier

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

Table of Contents:

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
Created in BioRender.com

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‡

Created in BioRender.com

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.

References

  1. Center for Disease Control and Prevention. June 21, 2024. Accessed January 19, 2025. https://www.cdc.gov.
  2. Fusco W, Lorenzo MB, Cintoni M, et al. Nutrients. 2023;15(9). doi:10.3390/nu15092211
  3. Di Sabatino A, Santacroce G, Rossi CM, Broglio G, Lenti MV. Intern Emerg Med. 2023;18(6). doi:10.1007/s11739-023-03329-1
  4. Ghosh S, Whitley CS, Haribabu B, Jala VR. CMGH. 2021;11(5). doi:10.1016/j.jcmgh.2021.02.007
  5. Khan I, Ullah N, Zha L, et al. Pathogens. 2019;8(3). doi:10.3390/pathogens8030126
  6. Ullah H, Arbab S, Tian Y, et al. Front Immunol. 2024;15:1413485. doi:10.3389/fimmu.2024.1413485
  7. Tanoue T, Umesaki Y, Honda K. Gut Microbes. 2010;1(4). doi:10.4161/gmic.1.4.12613
  8. De Castro MM, Pascoal LB, Steigleder KM, et al. World J Exp Med. 2021;11(1). doi:10.5493/wjem.v11.i1.1
  9. Christensen C, Knudsen A, Arnesen EK, Hatlebakk JG, Sletten IS, Fadnes LT. Advances in Nutrition. 2024;15(5):100219. doi:10.1016/j.advnut.2024.100219
  10. Balestrieri P, Ribolsi M, Guarino MPL, Emerenziani S, Altomare A, Cicala M. Nutrients. 2020;12(2). doi:10.3390/nu12020372
  11. Edman JS, Greeson JM, Roberts RS, et al. Explore: The Journal of Science and Healing. 2017;13(2). doi:10.1016/j.explore.2016.12.005
  12. Irwin MR, Opp MR. Neuropsychopharmacology. 2017;42(1). doi:10.1038/npp.2016.148
  13. Abbasi F, Haghighat Lari MM, Khosravi GR, Mansouri E, Payandeh N, Milajerdi A. Amino Acids. 2024;56(1):60. doi:10.1007/s00726-024-03420-7
  14. Kim MH, Kim H. Int J Mol Sci. 2017;18(5). doi:10.3390/ijms18051051
  15. Cao Y, Shen J, Ran ZH. Gastroenterol Res Pract. 2014;2014. doi:10.1155/2014/872725
  16. Dion C, Chappuis E, Ripoll C. Nutr Metab (Lond). 2016;13(1). doi:10.1186/s12986-016-0086-x
  17. Pressi G, Rigillo G, Governa P, et al. Pharmaceutics. 2023;15(1). doi:10.3390/pharmaceutics15010240
  18. Buchwald-Werner S, Fujii H, Reule C, Schoen C. BMC Complement Altern Med. 2014;14. doi:10.1186/1472-6882-14-173
  19. Takano H, Osakabe N, Sanbongi C, et al. Exp Biol Med. 2004;229(3). doi:10.1177/153537020422900305
  20. Adam G, Robu S, Flutur MM, et al. Antioxidants. 2023;12(3). doi:10.3390/antiox12030727
  21. Wang XY, Wang RC, Qu ZY, Zhu YZ, Li YL. Frontiers in Natural Products. 2022;1. doi:10.3389/fntpr.2022.971679
  22. Liang H, Tao S, Wang Y, et al. Front Nutr. 2024;11. doi:10.3389/fnut.2024.1364739
  23. Park HJ, Hyun YK, Yoon KH, Kyung SK, Shim I. Korean Journal of Physiology and Pharmacology. 2009;13(4). doi:10.4196/kjpp.2009.13.4.315
  24. Murray MT. In:Textbook of Natural Medicine.; 2020. doi:10.1016/b978-0-323-43044-9.00085-6
Blog

The 3 Stages of GI Dysfunction

  • May 14, 2022
Pure Encapsulations Pro Blog
Man listening to female doctor in office

The 3 Stages of GI Dysfunction

Webinar: “Functional GI Concerns: Understanding and Addressing the Root Cause” with Dr. Daniel Kalish, D.C.+

Associated material: PureGI Exclusive, PureGI Brochure


VIEW THE WEBINAR


A roadmap to help you understand and support gut health.

Why Focus on Gut Health for All Patients?

Complaints related to gastrointestinal (GI) health are highly prevalent in both US and global populations—with one academic survey reporting 61% of Americans experienced at least one GI symptom in the past week.1

GI complaints are not only common but often present in patients with structurally healthy GI tracts. In these cases, patient complaints are typically attributed to functional GI factors, such as alterations in the gut microbiota, immune function, and central nervous system processing.2

Due to the high rate of prevalence and discomfort associated with GI complaints (e.g., gas, bloating, abdominal discomfort, etc.), there is a great need for practitioners to understand and support functional GI factors—and in turn patient health and comfort.

Dr. Daniel Kalish, D.C.,+ founder of the Kalish Institute and practicing functional medicine thought leader, says, “Patient-reported GI complaints don’t manifest overnight. Instead, they develop over months or even years and progress through a predictable series of stages.”

This clinical observation, and a detailed understanding of the latest research, has led Dr. Kalish to this current model for understanding functional GI factors—the Three Stages of GI Function.

Stage One: Impact on Microbiome Health & Immune Activity

The first stage in the Three Stages of GI Function address lifestyle factors such as nutrition, sleep, and stress, which can lead to immune activation and changes in the gut microbiome. In this first stage, patient complaints are typically mild but, if not addressed, may advance.

  • Nutrition—When a patient complains of GI issues, the first place to look is their diet. Higher intake of animal foods, processed foods, alcohol, and sugar, corresponds to a microbial environment that is characteristic of inflammation, and is associated with higher levels of intestinal inflammatory markers.3
  • Sleep—Sleep deprivation is pervasive across the country, with the CDC reporting 35.2% of US adults are getting less than the recommended hours of sleep each night.4 Animal studies show that chronic sleep fragmentation for 4 weeks affects activities that can influence optimal gut function, such as increased food intake.5
  • Stress—Stress has been shown to alter the composition of the gut microbiota, causing it to skew away from beneficial bacteria towards an unhealthy imbalance.6

Stage Two: Impact in GI Organ & Immune System Function

Over time, prolonged activation of the immune system and shift in the gut microbiome (stage 1) can lead to changes in GI organ and immune system function. Patient complaints may become more diverse or intense at this stage.

  • Pancreas—Shifts in the gut microbiome have been associated with alterations in pancreatic activity, including enzyme production, which helps to regulate healthy gut activity.7
  • Bile—Microbial changes can also disrupt production and secretion of bile acids, since gut microbiota is integral to their metabolic processes.8
  • Immune—Connections between microbiome homeostasis and optimal immune health are well characterized. Specifically, immune balance can be altered through changes in T-helper cell polarization patterns.9

Stage Three: Impact on GI Microbial Defenses

Changes in the functionality of GI organs and immune function (stage 2) often influences GI microbial defenses (stage 3). Stomach acid, pancreatic enzymes and bile not only help us digest food but protect us from foreign microbes that we ingest, and a balanced immune system helps the body manage microbes already residing in our GI tract. In stage 3, patients may complain of worsening symptoms.

Middle-aged woman experiencing gut pain

Summary and Conclusion

Lifestyle factors such as diet, food sensitivities, stress, social isolation, lack of sleep, inactivity and many others can lead to immune activation and changes in the gut microbiome. This is the first stage in the Three Stages of GI Function, when complaints are typically mild but, if not addressed, may advance.

Over time, this prolonged, activation of the immune system and shift in the gut microbiome (stage 1) can lead to changes in GI organ and immune system function (stage 2). In this stage, basic digestive functions can be affected, such as stomach acidity, pancreatic enzyme and bile production, gut barrier integrity and others. Immune balance can also be altered through changes in T-helper cell polarization patterns. Patient complaints may become more diverse.

Changes in the functionality of GI organs and immune function (stage 2) often influences GI microbial defenses (stage 3). Stomach acid, pancreatic enzymes and bile not only help us digest food but protect us from foreign microbes that we ingest, and a balanced immune system helps the body manage microbes already residing in our GI tract. In stage 3, patients may complain of worsening symptoms.

It is important to note that Three Stages of GI Function is a self-perpetuating process. While lifestyle factors often initiate it, stages 2 and 3 loop back into stage 1, further affecting microbiome health and immune activity.

Dr. Kalish concludes, “In natural medicine, the GI tract is considered the ‘mother’ of the body—meaning, it feeds and heals the rest of the organ systems. A complete workup for any chief complaint must include a thorough GI assessment.”

Works Cited

  1. Almario CV, Ballal ML, Chey WD, et al. Am J Gastroenterol. 2018;113(11):1701-1710.
  2. Sperber AD, Bangdiwala SI, Drossman DA, et al. Gastroenterology. 2021 Jan;160(1):99-114.e3.
  3. Bolte LA, Vich Vila A, Imhann F, et al. Gut. 2021 Jul;70(7):1287-1298.
  4. https://www.cdc.gov/sleep/data_statistics.html
  5. Poroyko VA, Carreras A, Khalyfa A, et al. Sci Rep. 2016 Oct 14;6:35405.
  6. Gao X, Cao Q, Cheng Y, et al. Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):E2960-E2969.
  7. Akshintala VS, Talukdar R, Singh VK, Goggins M. Clin Gastroenterol Hepatol. 2019;17(2):290-295
  8. Wang C, Zhu C, Shao L, Ye J, Shen Y, Ren Y. Mediators Inflamm. 2019 Jun 24;2019:7659509.
  9. Zheng D, Liwinski T, Elinav E. Cell Res. 2020 Jun;30(6):492-506.
  10. Iacob S, Iacob DG. Front Microbiol. 2019 Aug 7;10:1676.

+Dr. Daniel Kalish, M.D., is a retained advisor for Pure Encapsulations®.

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