Intestinal Permeability and Inflammatory Triggers

allergic food on a white wooden background.
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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:

[Video Time: 1 minute.] Dr. Sheeler is board certified in family medicine, holistic medicine, integrative medicine, and headache medicine and is a certified functional medicine practitioner. He has also lectured extensively both nationally and internationally on headache disorders, combining traditional and integrative medicine approaches.

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

Celiac Disease

  • Autoimmune diseases
  • Osteoporosis
  • Epilepsy
  • Infertility
  • Depression
  • Tooth enamel defects, etc.

Non-Celiac Gluten/Wheat Sensitivity

  • Fatigue
  • Headache
  • Joint or bone pain
  • Skin manifestations such as rash or eczema
  • Mood disorders, etc.

Wheat Allergy

  • Eczema
  • Hives, urticaria
  • Asthma
  • Rhinitis
  • 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.

Learn More About gut Dysfunction and Chronic Conditions

Related Articles

Framework for Treating GI Issues

The Role of Microbiome in Immune-Related Diseases

Treating the Underlying Causes of Chronic Migraine

Non-Celiac Immune Responses to Gluten


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