Intestinal Permeability and Inflammatory Triggers
Read Time: 5 Minutes
Optimal gastrointestinal (GI) health plays a vital role for robust immunity and overall wellness. Increasingly, research studies associate imbalances in the gut to diseases that may not at first seem connected to gut function. Work by several researchers has linked intestinal permeability to chronic respiratory allergies/rhinitis,1 asthma,2 and eczema.3 Furthermore, intestinal dysbiosis is known to play a role in many autoimmune conditions and other chronic diseases,4 and reactions to foods often have symptoms that manifest far from the intestines.
One of the common consequences of food reactions can be headaches and migraines. Headache specialist Robert Sheeler, MD, IFMCP, describes the many types of symptoms that can manifest in the presence of food reactions:
Eczema and the Gut
As Dr. Sheeler states, food reactions can sometimes take the form of rashes or skin problems. On first glance, the connection between intestinal mucosal disruption and eczema may seem the most straightforward; skin microbiome5 and barrier integrity6 are known to be affected in patients with eczema, and the connection between the skin microbiome and the gut microbiome seems intuitive.
Indeed, evidence is accumulating that treatments aimed at restoring balance in the gut microbiome, such as ingesting probiotics, may reduce eczema,7 and that the use of prebiotics and probiotics early in life may play a role in eczema prevention.8,9 However, a 2018 Cochrane Review of 39 randomized controlled trials found that probiotic treatments only slightly reduced eczema severity in patients.10 Another approach, removing inflammatory environmental triggers, may be more effective.11
Headaches, Migraines, and Food Reactions
Individuals with chronic gastrointestinal symptoms are more likely to have headaches or migraines.12 The pro-inflammatory immune response associated with intestinal permeability likely plays a role in increasing headache and migraine frequency.
Many patients who suffer from migraines or chronic headaches state that it seems to them like dietary factors are involved.13,14 Dietary triggers tend to be personalized, and interventions need to emphasize overall healthy lifestyle change rather than simply food restriction.15 However, research suggests that certain classes of food may be more likely to trigger headaches. For example, an observational study of 115 children with chronic headaches excluded caffeine, MSG, cocoa, aspartame, cheese, citrus, and nitrates for six weeks.16 At the six-week mark, 87% of the children no longer suffered from headache.16 Of important note, this observational study did not follow up with reintroduction of foods to identify which foods may have been the specific triggers for each individual.16
While the mechanisms are not completely understood, IgG-mediated food allergies and the resulting inflammatory response may play an important role in the presentation and frequency of migraine symptoms.17 Studies have examined how IgG antibody testing may guide exclusion of certain foods, showing a reduction in headaches when foods found to be positive on testing were eliminated.17-19 A 2019 double-blind randomized controlled cross-over clinical trial investigated the therapeutic potential of an IgG elimination diet combined with probiotics for treatment of migraine and irritable bowel syndrome.17 Results suggested a decrease in migraine frequency for those subjects following the IgG elimination diet and those on the diet plus probiotics.17
Non-GI Symptoms of Non-Celiac Gluten Sensitivity, Wheat Allergy, & Celiac Disease
The ingestion of gluten has been linked to several clinical disorders beyond the autoimmune condition known as celiac disease (CD), including wheat allergy and non-celiac gluten/wheat sensitivity (NCGS). NCGS is considered an immune system–related disease,20 and while increased intestinal permeability after gluten consumption is noted in people with CD, there is conflicting data on whether the epithelial barrier is a pathogenic cofactor for the development of NCGS.21 However, a 2016 study suggested that intestinal epithelial barrier impairment may lead to increased microbial translocation and systemic immune responses,22 which in turn may contribute to the pathophysiology of NCGS.21
Changes in the gut microbiome produced by gluten consumption may also influence NCGS pathophysiology.23 The potential GI and systemic inflammation resulting from gut dysbiosis may help to explain the variety of NCGS clinical presentations.23,24 In addition to GI symptoms, a wide range of extra-intestinal symptoms have been associated with not only NCGS, but also CD and wheat allergy, suggesting systemic manifestations of the conditions.
While there are many manifestations of these conditions and overlaps between them, the following is a sample of noted extra-intestinal symptoms:20,25-27
- Autoimmune diseases
- Tooth enamel defects, etc.
Non-Celiac Gluten/Wheat Sensitivity
- Joint or bone pain
- Skin manifestations such as rash or eczema
- Mood disorders, etc.
- Hives, urticaria
- Anaphylaxis, etc.
Clinical Application: Practical Steps
Identifying and treating inflammatory environmental triggers that create or perpetuate GI inflammation and imbalance can be challenging, due to the range of potential symptoms. Functional medicine tools such as the matrix and timeline are used to map out the patient’s health journey, organize their clinical imbalances, and help develop a personalized treatment strategy. These strategies may include the removal of potential triggers, the use of therapeutic food plans and nutraceuticals, and addressing modifiable lifestyle factors for an overall health lifestyle change.
For food reactions, specifically, dietary triggers may be highly specific to the individual and include compounding variables such as cross-reactivity. In addition, if a patient restricts certain foods, such as gluten, without proper nutritional counseling, this may lead to an unbalanced diet with less than optimal nutrient density and exacerbate health concerns. Functional medicine tools help manage any potential nutritional issue that may arise from following a therapeutic diet by guiding patients through the process, highlighting nutrients of concern, and addressing how patients can access specific nutrients through food or supplementation.
In addition to removing potential trigger foods, IFM recommends supporting gut health by reducing inflammation, improving nutritional status, and supporting the microbiome with pre- and/or probiotics. These steps can help reduce immune activation and lead to overall improved health, beyond reducing the symptoms. Learn more about improving gastrointestinal health at IFM’s GI Advanced Practice Module.
Framework for Treating GI Issues
The Role of Microbiome in Immune-Related Diseases
Treating the Underlying Causes of Chronic Migraine
- Steelant B, Farré R, Wawrzyniak P, et al. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol. 2016;137(4):1043-1053.e5. doi:10.1016/j.jaci.2015.10.050
- Hijazi Z, Molla AM, Al-Habashi H, Muawad WM, Molla AM, Sharma PN. Intestinal permeability is increased in bronchial asthma. Arch Dis Child. 2004;89(3):227-229. doi:10.1136/adc.2003.027680
- Sheen YH, Jee HM, Kim DH, et al. Serum zonulin is associated with presence and severity of atopic dermatitis in children, independent of total IgE and eosinophil. Clin Exp Allergy. 2018;48(8):1059-1062. doi:10.1111/cea.13158
- van der Meulen TA, Harmsen H, Bootsma H, Spijkervet F, Kroese F, Vissink A. The microbiome-systemic diseases connection. Oral Dis. 2016;22(8):719-734. doi:10.1111/odi.12472
- Paller AS, Kong HH, Seed P, et al. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):26-35. doi:10.1016/j.jaci.2018.11.015
- Wollina U. Microbiome in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:51-56. doi:10.2147/CCID.S130013
- Lu CL, Liu XH, Stub T, et al. Complementary and alternative medicine for treatment of atopic eczema in children under 14 years old: a systematic review and meta-analysis of randomized controlled trials [published correction appears in: BMC Complement Altern Med. 2019;19(1):16]. BMC Complement Altern Med. 2018;18(1):260. doi:10.1186/s12906-018-2306-6
- Szari S, Quinn JA. Supporting a healthy microbiome for the primary prevention of eczema. Clin Rev Allergy Immunol. 2019;57(2):286-293. doi:10.1007/s12016-019-08758-5
- Schmidt RM, Pilmann Laursen R, Bruun S, et al. Probiotics in late infancy reduce the incidence of eczema: a randomized controlled trial. Pediatr Allergy Immunol. 2019;30(3):335-340. doi:10.1111/pai.13018
- Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev. 2018;11(11):CD006135. doi:10.1002/14651858.CD006135.pub3
- Kantor R, Silverberg JI. Environmental risk factors and their role in the management of atopic dermatitis. Expert Rev Clin Immunol. 2017;13(1):15-26. doi:10.1080/1744666X.2016.1212660
- Dai YJ, Wang HY, Wang XJ, Kaye AD, Sun YH. Potential beneficial effects of probiotics on human migraine headache: a literature review. Pain Physician. 2017;20(2):E251-E255.
- Finocchi C, Sivori G. Food as trigger and aggravating factor of migraine. Neurol Sci. 2012;33(Suppl 1):S77-S80. doi:10.1007/s10072-012-1046-5
- Marmura MJ. Triggers, protectors, and predictors in episodic migraine. Curr Pain Headache Rep. 2018;22(12):81. doi:10.1007/s11916-018-0734-0
- Slavin M, Ailani J. A clinical approach to addressing diet with migraine patients. Curr Neurol Neurosci Rep. 2017;17(2):17. doi:10.1007/s11910-017-0721-6
- Taheri S. Effect of exclusion of frequently consumed dietary triggers in a cohort of children with chronic primary headache. Nutr Health. 2017;23(1):47-50. doi:10.1177/0260106016688699
- Xie Y, Zhou G, Xu Y, et al. Effects of diet based on IgG elimination combined with probiotics on migraine plus irritable bowel syndrome. Pain Res Manag. 2019;2019:7890461. doi:10.1155/2019/7890461
- Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829-837. doi:10.1177/0333102410361404
- Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache. 2013;53(3):514-525. doi:10.1111/j.1526-4610.2012.02296.x
- Losurdo G, Principi M, Iannone A, et al. Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm. World J Gastroenterol. 2018;24(14):1521-1530. doi:10.3748/wjg.v24.i14.1521
- Cardoso-Silva D, Delbue D, Itzlinger A, et al. Intestinal barrier function in gluten-related disorders. Nutrients. 2019;11(10):E2325. doi:10.3390/nu11102325
- Uhde M, Ajamian M, Caio G, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65(12):1930-1937. doi:10.1136/gutjnl-2016-311964
- Igbinedion SO, Ansari J, Vasikaran A, et al. Non-celiac gluten sensitivity: all wheat attack is not celiac. World J Gastroenterol. 2017;23(40):7201-7210. doi:10.3748/wjg.v23.i40.7201
- Morris G, Berk M, Carvalho AF, Caso JR, Sanz Y, Maes M. The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on inflammatory bowel disease type 1 diabetes and chronic fatigue syndrome. Curr Pharm Des. 2016;22(40):6058-6075. doi:10.2174/1381612822666160914182822
- Popp A, Mäki M. Gluten-induced extra-intestinal manifestations in potential celiac disease—celiac trait. Nutrients. 2019;11(2):320. doi:10.3390/nu11020320
- Ricci G, Andreozzi L, Cipriani F, Giannetti A, Gallucci M, Caffarelli C. Wheat allergy in children: a comprehensive update. Medicina (Kaunas). 2019;55(7):400. doi:10.3390/medicina55070400
- Elli L, Branchi F, Tomba C, et al. Diagnosis of gluten related disorders: celiac disease, wheat allergy and non-celiac gluten sensitivity. World J Gastroenterol. 2015;21(23):7110-7119. doi:10.3748/wjg.v21.i23.7110