Allergies and autoimmune diseases are increasing rapidly in the developed world. There are at least three related theories to explain this.  

  • The “hygiene hypothesis” notes that children protected from germs and parasites end up vulnerable, as their immune systems don’t “learn” to distinguish friend from foe.
  • We are exposed to a wide range of chemicals in the air, food, and water: microplastics, ozone, pesticides, exhaust fumes, cigarette smoke, and more. These substances weaken the special, sheet-like tissue called epithelium that lines our stomach, esophagus and intestines. The idea that damage to this tissue can trigger allergies is sometimes called the “epithelial barrier hypothesis.” Toxic exposures may also explain autoimmune illness. If the lining of the intestine is weakened, a condition called “intestinal permeability” or “leaky gut,” it can’t completely do its job of protecting the gut. The altered environment sets off systemic chronic immune reactions.
  • Our diet of increasingly hyperprocessed foods is changing the balance of microorganisms in our bodies, collectively known as the microbiome, which harms efficient immune function.
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This rendering of a “leaky” intestinal junction shows how broken-down food particles that should remain within the digestive tract can escape into the vascular system. Antibodies interpret the particles as pathological invaders, ramping up inflammation to chronic, unhealthy levels.

Put this all together, some say, and leaky guts combined with intestinal imbalance may contribute not only to autoimmune illness to other diseases afflicting Americans like diabetes, obesity, Alzheimer’s, autism spectrum disorder and depression (Bodenmueller, 2021)_(Akdis, 2021).  

The good news is that consuming omega-3s plentiful in fatty fish appears to help protect us. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are incorporated into the cell membrane, helping to prevent it from becoming too permeable or leaky (Durkin et al., 2021).

The rise of allergies and autoimmune illness in modern life

Have you ever wondered what hay-fever has to do with hay? This allergic reaction arose in the 1800s when farmers introduced grasses to make hay for dairy herds. Ragweed sprang up in the United States around newly-plowed fields and seasonal stuffy noses became common by the end of the century.

The trouble accelerated. Hospital admissions of children with asthma increased tenfold between 1965 and 1980. Since 2000, industrialized countries have seen a flare-up in food allergy and drug reactions. Specific food allergy antigens were rarely found in blood samples in the 1970s and 1980s, but by 2018, almost all babies tested showed evidence of allergies to milk and egg. Currently, half the population in Europe, the United States, Canada and Australia has at least one allergy (Akdis, 2021).

One clear sign that we can blame something about how we live: although East Germans had few allergies in 1989, they developed similar problems as West Germans have after reunification, presumably because of increased access to Western diets and lifestyles.

Scientists have attributed this steady increase to everything from Caesarean delivery (which deprives newborns of exposure to the mother’s protective microorganisms in the vagina) and early use of antibiotics (which leave the gut unbalanced), to the Western diet and obesity.

Others have theorized that smaller families play a role. Children born into a household with many siblings are less likely to develop eczema in their first year and hay fever as they age. The “hygiene hypothesis” points to the fact that better hygiene and smaller families have protected us from parasites and childhood infections, but we may need those challenges to develop mature immune systems, ones that can distinguish true threats from benign microbes.

Children
The hygiene hypothesis holds that kids who have many siblings, pets and spend time outdoors benefit because their immune systems learn which microbes are harmful and which are benign.

It’s rather like needing some hard knocks in life to know when a problem really isn’t such a big deal and choosing our battles well. (Bach 2021, 2017).

However, the hygiene hypothesis, while it may help explain part of the problem, doesn’t explain why allergies are increasing in some cities in Africa and Asia that do not have modern hygiene. The problem also need not start in childhood. Adults who move from developing countries to richer ones tend to rapidly develop asthma, allergies and autoimmune illness as well (Akdis, 2021).

So what’s the most fundamental cause? Increasingly, researchers are focusing on the gut.

What you didn’t know about your gut

The gut barrier is the largest interface separating any part of our “insides” from the outside world.

The epithelial cells that line the gut take up nutrients and water, and regulate other responses to nearby cells, communicating with gut bacteria and intestinal immune cells (Akdis, 2021). But epithelial cells move and change shape, and sometimes the junctions between them can develop gaps. A built-in system triggers local repairs to keep the barrier consistent. You can see this process in action (in a frog embryo) here. (Erickson, 2019).

If these repairs aren’t made, the gut becomes vulnerable. This may happen, for example, when the gut epithelial cells are exposed to chemicals as common as emulsifiers in processed food in small amounts (Akdis, 2021).

Overall our diet affects how well the barrier functions. Vitamins C, D3, and E, flavonoids (See "Eat the Rainbow" for a description of these nutrients in fruits and vegetables), the short-chain fatty acids that digest fiber, and some polyunsaturated fatty acids, including omega-3s, all appear to protect it —and thus affect our immunity.

As readers of our newsletter know, the best way to get EPA and DHA omega-3s is by eating seafood, especially fish like salmon, mackerel and sardines. You can also take fish oil supplements.

(A third, often-recommended course is to consume alpha-linolenic acid, or ALA, through flaxseeds, walnuts, canola or soybean oil, which your body must convert to EPA and then DHA, but this process is highly inefficient and no substitute for consuming seafood.)

A recent overview of more than 80 studies analyzing the effect of these fatty acids on inflammatory bowel disease or inflammation markers concluded that increasing consumption of omega-3s for at least six months can cut the risk of a relapse or worsening case (Ajabnoor et al., 2020).

Beyond the gut

Epithelial damage from everyday chemicals may accumulate. In the past 20 years, researchers at the Swiss Institute of Allergy and Asthma Research linked to the University of Zurich have investigated how various substances damage the protective epithelial cells of a number of organs. Not just the gut but the skin and upper and lower airways are affected.

For example, common ingredients in laundry detergent, soap and shampoo disrupt the epithelial layer of the skin and bronchial tubes even when highly diluted, reports Director Cezmi Akdis, who is also editor of the journal Allergy (Akdis, 2021). He notes research showing that nurses exposed to medical disinfectant tended toward asthma.

Microorganisms settle in tissues behind leaky epithelial tissue, where they displace friendly bacteria and trigger inflammation, setting off bad feedback loops, Akdis explains. Stimulated by the altered environment, immune T cells can overreact throughout the body, such as when children sensitive to milk develop skin rashes. Germs like staphylococcus aureus get behind the barrier in the skin and nose and overgrow, also aggravating asthma and rashes.

Bottom line

What can you do about all this? Let’s say you react badly to wheat, even though you don’t have the autoimmune problem celiac disease. Research suggests that you may have a leaky gut triggering an inflammatory reaction (Uhde, 2016).

Besides avoiding wheat, you could think about your chronic chemical exposures and try to limit them. You could also see your wheat problem as a sign that you need a better overall diet, including more omega-3s, ideally from marine sources like salmon and shellfish.

The good news is, a battered epithelium wants to repair itself. Give it the right diet and environment, and it can begin to do so.

 

Sources:

Ajabnoor, S. M., Thorpe, G., Abdelhamid, A., & Hooper, L. (2021). Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials. European journal of nutrition, 60(5), 2293–2316. https://doi.org/10.1007/s00394-020-02413-y  E-published October 21, 2020.

Akdis C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nature reviews. Immunology, 10.1038/s41577-021-00538-7. https://doi.org/10.1038/s41577-021-00538-7 Published April 12, 2021.

Bach J. F. Revisiting the Hygiene Hypothesis in the Context of Autoimmunity. Frontiers in immunology, 11, 615192. https://doi.org/10.3389/fimmu.2020.615192  Published January 28, 2021.

Bach J. F. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nature reviews. Immunology, 18(2), 105–120. https://doi.org/10.1038/nri.2017.111 E-published October 16, 2017.

Bodenmueller, K.  Team links LEAKY Epithelial barriers to 2 Billion chronic diseases. Futurity. https://www.futurity.org/epithelial-barriers-chronic-diseases-2561192/. Published May 7, 2021.

Durkin LA, Childs CE, Calder PC. Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium-A Review. Foods. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835870/ Published January 19, 2021.

Erickson J. Watch 'flares' repair leak in protective cell barrier. Futurity. https://www.futurity.org/epithelial-tissues-organs-barrier-1984642/. Published February 15, 2019.

Krämer, U., Schmitz, R., Ring, J., & Behrendt, H. What can reunification of East and West Germany tell us about the cause of the allergy epidemic?. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 45(1), 94–107. https://doi.org/10.1111/cea.12458 Published January, 2015.

Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P. H., Verna, E. C., Volta, U., & Alaedini, A. (2016). Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut, 65(12), 1930–1937. https://doi.org/10.1136/gutjnl-2016-311964   E-publushed July 25, 2016.