Gut Barrier Panel

The Gut Barrier Panel offered by KMBO Diagnostics detects the presence of leaky gut by providing an assessment of the integrity of the gut barrier.  

Operating from the awareness that leaky gut occurs along a spectrum, KMBO has developed the Gut Barrier Panel to assess for IgG 1-4 /C3d and IgA 1-2 immune responses to these four gatekeeper markers: zonulin, candida, occludin, and LPS (lipopolysaccharide).  

Using a patented multiple pathway approach that includes measurements of  IgG1-4 and complement activation via the marker C3d, this test accurately indicates inflammation at the gut lining.  

Additionally, the Gut Barrier Panel specifically targets leaky gut by using a proprietary Zonulin assay.

This is the blood spot version of the test. 

What is the Clinical Significance of IgA 1 + 2 Antibody Testing?

IgA 1 and IgA 2 testing holds clinical significance primarily in the context of assessing mucosal immunity and gut barrier function, and it may play a role in the development of immune tolerance.  [8., 12.]  

Immunoglobulin A (IgA) is the primary antibody found in mucosal secretions, including those of the gastrointestinal tract. IgA defends against pathogens and antigens present in the gut, as well as in maintaining the integrity of the gut epithelium and developing immune tolerance to beneficial gut microbes.  [8.]

Dysregulation of mucosal immunity, characterized by alterations in IgA production, has been implicated in various gastrointestinal disorders, including inflammatory bowel diseases, celiac disease, and irritable bowel syndrome. [18.]

By measuring IgA 1 and IgA 2 levels, healthcare providers can gain insights into the status of mucosal immunity, the integrity of the gut barrier, and immune activity in the GI tract. 

Abnormalities in IgA levels may indicate disruptions in gut barrier function, increased intestinal permeability (leaky gut), or heightened immune responses to dietary antigens, all of which can contribute to gastrointestinal symptoms and systemic inflammation.

What is the Clinical Significance of IgG 1-4 Antibody Testing?

The Gut Barrier Panel by KBMO Diagnostics employs testing for all four IgG antibody subclasses: IgG 1-4.  IgG antibodies 1-3 activate a branch of the innate immune system called complement, which stimulates an inflammatory response.  In contrast, IgG 4 does not have this capability.  

Accumulating evidence suggests that IgG antibody testing may shed light for clinicians.  [6., 17., 20.]  For example, some studies indicate that IgG-mediated immune responses might contribute to the pathogenesis of gastrointestinal inflammation.  [7., 18.]  

By detecting IgG antibodies to specific food antigens, the Gut Barrier Panel by KBMO Diagnostics aims to identify potential triggers for immune-mediated reactions and provide insights into personalized dietary modifications to alleviate symptoms and improve overall health outcomes.

IgG4, a subtype of immunoglobulin G antibodies, plays a crucial role in modulating immune responses, particularly in the context of allergies. Research indicates that IgG4 antibodies can help neutralize allergic reactions orchestrated by IgE, thereby mitigating histamine responses and promoting immune tolerance to foods.  

It's essential to maintain a balanced level of IgG4, as excessive amounts can paradoxically lead to increased inflammation and immune sensitization.  Increased IgG4 levels have been associated with allergies and with autoimmune conditions.  For instance, elevated IgG4 levels have been implicated in conditions such as rheumatoid arthritis, myasthenia gravis, pemphigus vulgaris and thrombotic thrombocytopenic purpura. [11., 13., 16.]

What is the Clinical Significance of C3d Testing for Food Sensitivities? 

C3d (Complement Component 3) is a protein of the innate immune system that can promote an inflammatory response.  The inclusion of complement proteins C3d in the Gut Barrier Panel by KBMO Diagnostics provides a more comprehensive assessment of the immune response to dietary antigens. 

Complement proteins play a crucial role in the immune cascade triggered by IgG-mediated reactions. Specifically, C3d is involved in the opsonization of immune complexes, facilitating their recognition and clearance by phagocytic cells; their role can increase the actions of IgG antibodies many times over. By measuring levels of C3d alongside IgG antibodies against common foods, this test offers valuable insights into the inflammatory response associated with food sensitivities.

Complement activation, particularly through the C3d pathway, may contribute to the pathogenesis of various immune-mediated disorders, including food sensitivities and allergic reactions.  [22.]

What is the Clinical Significance of Testing the Following Leaky Gut Markers:

Candida

Blood testing for Candida can provide insights into potential Candida overgrowth and dysbiosis, which can manifest as gastrointestinal symptoms and contribute to various health issues. Candida is a type of yeast normally found in the human gut microbiota, but overgrowth can occur due to factors such as immune system dysfunction, antibiotic use, or dietary factors, causing or worsening leaky gut.  [1.]

Zonulin

KBMO Diagnostics now includes a unique Zonulin assay in the Gut Barrier Panel which features a novel recombinant zonulin protein, ensuring no cross-reactivity with haptoglobin, properdin, or complement fragments, while maintaining stability to avoid assay fluctuations. 

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Zonulin, a key biomarker for intestinal permeability, complements the Gut Barrier Panel’s ability to diagnose leaky gut alongside other leaky gut markers. Elevated Zonulin antibody levels are associated with IBD and autoimmune conditions, making it a valuable marker for assessing gut health and guiding treatment strategies.  [4., 9.]

Occludin

Blood testing for occludin antibodies serves as a valuable tool in assessing intestinal permeability or "leaky gut" syndrome. Elevated levels of occludin antibodies indicate disruption of tight junctions between intestinal cells, allowing harmful substances to pass through the gut barrier. 

By signaling the potential for damage at the level of the gut barrier, this testing aids in diagnosing leaky gut and guides treatment strategies aimed at restoring gut barrier integrity and reducing systemic inflammation.  [5.]

LPS, or Lipopolysaccharides

Testing for lipopolysaccharide antibodies in leaky gut provides valuable clinical insight into gut barrier dysfunction and systemic inflammation. Elevated levels of lipopolysaccharide antibodies indicate increased permeability of the gut lining, allowing bacterial endotoxins to enter the bloodstream and trigger immune responses. 

This testing aids in diagnosing leaky gut and guides treatment approaches focused on restoring gut barrier function, addressing dysbiosis, and reducing inflammation. [21.]

Who Can Benefit from the Gut Barrier Panel by KBMO Diagnostics?

Individuals Seeking to Optimize Health: even in the absence of symptoms, the Gut Barrier Panel can offer insights into gut health, providing an opportunity for preventative measures against potential health issues and supporting the body’s natural health by optimizing digestion.

Patients with Chronic Digestive Dysfunction: for those who have suffered from chronic symptoms with or without a clear diagnosis, the Gut Barrier Panel can help identify underlying inflammation in the gut that may be contributing to their health issues.

Autoimmune Diseases: since gut health is closely linked to the immune system, identifying and addressing leaky gut can provide additional treatment options and provide crucial support in managing autoimmune conditions. [15].

Gastrointestinal Disorders: for patients struggling with Small Intestinal Bowel Overgrowth (SIBO), Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD), the Gut Barrier Panel by KBMO Diagnostics can identify previously-silent leaky gut that may be contributing to symptoms like gas, bloating, diarrhea, and constipation. [3., 14.]

Digestive Complaints: people experiencing unexplained digestive issues such as gas, bloating, heartburn, indigestion, diarrhea, or constipation can identify potential causes and receive targeted treatment recommendations.  [14.] 

Neurological and Cognitive Issues: the vagus nerve is the primary nerve that innervates the digestive tract, and is considered the “highway of the gut-brain axis”.  Insights into the gut-brain axis through the Gut Barrier Panel may reveal how gut health impacts an individual’s cognitive function and affects memory, concentration, and brain fog. [5.]

Skin Conditions: conditions like acne and psoriasis have been linked to gut health. Identifying and treating leaky gut can be a part of a comprehensive treatment plan to improve and restore skin health. [10.]

Mood Disorders: the gut-brain connection means that digestive inflammation can impact mood and emotional well-being, making the Gut Barrier Panel by KBMO Diagnostics valuable for individuals with these conditions. [5.]

References:

[1.] Basmaciyan L, Bon F, Paradis T, Lapaquette P, Dalle F. "Candida Albicans Interactions With The Host: Crossing The Intestinal Epithelial Barrier". Tissue Barriers. 2019;7(2):1612661. doi: 10.1080/21688370.2019.1612661. Epub 2019 Jun 12. PMID: 31189436; PMCID: PMC6619947.

[2.] Brady DM. Molecular Mimicry, the Hygiene Hypothesis, Stealth Infections and Other Examples of Disconnect between Medical Research and the Practice of Clinical Medicine in Autoimmune Disease. Open Journal of Rheumatology and Autoimmune Diseases. 2013;03(01):33-39. doi:https://doi.org/10.4236/ojra.2013.31007 

[3.] Capobianco I, Di Vincenzo F, Puca P, Becherucci G, Mentella MC, Petito V, Scaldaferri F. Adverse Food Reactions in Inflammatory Bowel Disease: State of the Art and Future Perspectives. Nutrients. 2024 Jan 25;16(3):351. doi: 10.3390/nu16030351. PMID: 38337636; PMCID: PMC10857040. 

[4.] Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. 2011;91(1):151-175. doi:https://doi.org/10.1152/physrev.00003.2008

[5.] Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020 Jan 31;9:F1000 Faculty Rev-69. doi: 10.12688/f1000research.20510.1. PMID: 32051759; PMCID: PMC6996528. 

[6.] Geiselman JF. The Clinical Use of IgG Food Sensitivity Testing with Migraine Headache Patients: a Literature Review. Curr Pain Headache Rep. 2019 Aug 27;23(11):79. doi: 10.1007/s11916-019-0819-4. PMID: 31456119.

[7.] Gocki J, Bartuzi Z. Role of immunoglobulin G antibodies in diagnosis of food allergy. Postepy Dermatol Alergol. 2016 Aug;33(4):253-6. doi: 10.5114/ada.2016.61600. Epub 2016 Aug 16. PMID: 27605894; PMCID: PMC5004213.

[8.] Gutzeit C, Magri G, Cerutti A. Intestinal IgA production and its role in host-microbe interaction. Immunol Rev. 2014 Jul;260(1):76-85. doi: 10.1111/imr.12189. PMID: 24942683; PMCID: PMC4174397.

[9.] Heidt C, Kämmerer U, Fobker M, Rüffer A, Marquardt T, Reuss-Borst M. Assessment of Intestinal Permeability and Inflammation Bio-Markers in Patients with Rheumatoid Arthritis. Nutrients. 2023 May 19;15(10):2386. doi: 10.3390/nu15102386. PMID: 37242269; PMCID: PMC10221762. 

[10.] Katta R, Schlichte M. Diet and dermatitis: food triggers. J Clin Aesthet Dermatol. 2014 Mar;7(3):30-6. PMID: 24688624; PMCID: PMC3970830. 

[11.] Koneczny I. Update on IgG4-mediated autoimmune diseases: New insights and new family members. Autoimmunity Reviews. 2020;19(10):102646. doi:https://doi.org/10.1016/j.autrev.2020.102646

[12.] Konstantinou GN, Nowak-Węgrzyn A, Bencharitiwong R, Bardina L, Sicherer SH, Sampson HA. Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a role in tolerance induction? Pediatr Allergy Immunol. 2014 Feb;25(1):64-70. doi: 10.1111/pai.12143. Epub 2013 Oct 7. PMID: 24118158; PMCID: PMC4134474.

[13.] Maslinska M, Dmowska-Chalaba J, Jakubaszek M. The Role of IgG4 in Autoimmunity and Rheumatic Diseases. Front Immunol. 2022 Jan 25;12:787422. doi: 10.3389/fimmu.2021.787422. PMID: 35145508; PMCID: PMC8821096. 

[14.] Pasta A, Formisano E, Calabrese F, Plaz Torres MC, Bodini G, Marabotto E, Pisciotta L, Giannini EG, Furnari M. Food Intolerances, Food Allergies and IBS: Lights and Shadows. Nutrients. 2024 Jan 16;16(2):265. doi: 10.3390/nu16020265. PMID: 38257158; PMCID: PMC10821155. 

[15.] Paray BA, Albeshr MF, Jan AT, Rather IA. Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State. Int J Mol Sci. 2020 Dec 21;21(24):9770. doi: 10.3390/ijms21249770. PMID: 33371435; PMCID: PMC7767453.

[16.] Qin L, Tang LF, Cheng L, Wang HY. The clinical significance of allergen-specific IgG4 in allergic diseases. Front Immunol. 2022 Oct 25;13:1032909. doi: 10.3389/fimmu.2022.1032909. PMID: 36389804; PMCID: PMC9648126. 

[17.] Shakoor Z, AlFaifi A, AlAmro B, AlTawil LN, AlOhaly RY. Prevalence of IgG-mediated food intolerance among patients with allergic symptoms. Ann Saudi Med. 2016 Nov-Dec;36(6):386-390. doi: 10.5144/0256-4947.2016.386. PMID: 27920409; PMCID: PMC6074204.

[18.] Simeonova D, Ivanovska M, Murdjeva M, Carvalho AF, Maes M. Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays. Curr Top Med Chem. 2018;18(19):1641-1655. doi: 10.2174/1568026618666181115100610. PMID: 30430944.

[19.] Song DJ, Shen J, Chen MH, et al. Association of Serum Immunoglobulins Levels With Specific Disease Phenotypes of Crohn’s Disease: A Multicenter Analysis in China. Frontiers in Medicine. 2021;8. doi:https://doi.org/10.3389/fmed.2021.621337

[20.] Vita AA, Zwickey H, Bradley R. Associations between food-specific IgG antibodies and intestinal permeability biomarkers. Front Nutr. 2022 Sep 6;9:962093. doi: 10.3389/fnut.2022.962093. PMID: 36147305; PMCID: PMC9485556.

[21.] Vojdani A, Vojdani E, Herbert M, Kharrazian D. Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA. Int J Mol Sci. 2020 Feb 18;21(4):1381. doi: 10.3390/ijms21041381. PMID: 32085663; PMCID: PMC7073094. 

[22.] Yves Laumonnier, Rabia Ülkü Korkmaz, Nowacka AA, Jörg Köhl. Complement‐mediated immune mechanisms in allergy. European Journal of Immunology. 2023;53(10). doi:https://doi.org/10.1002/eji.202249979