Allergy

Allergy, the immune-gut interplay

Allergy is an ‘immunological hypersensitivity’, and as such is referred to as an ‘immune-mediated’ disease. Allergic diseases in infancy and childhood are an early signal that the immune system has created an inadequate response and therefore can be considered imbalanced.1 This could provide an indication of an increased risk of developing other non-communicable diseases later in life, such as diabetes and chronic respiratory diseases.2–8

Allergies occur when the immune system overreacts to substances that are usually harmless, such as foods, pollen, or pet dander. Early life, from pregnancy, through to infancy and childhood, presents an important window of opportunity to positively modify the developing immune system. A well developed immune system is of key importance to ensure the maintenance of health for infants and children, throughout life.2

Modern life challenges the developing immune system

The incidence of allergy is on the rise, with up to 40% of the world’s population now affected.2,3 It is thought the rising allergy epidemic is due to the vulnerability of the developing immune system to meet the challenges related to modern life.2 Although our immune systems have evolved to deal with changes in our environment, the world may be changing faster than our immune systems can adapt. These modern changes include pollution, the widespread use of antibiotics and increasing number of caeserian-section deliveries. Each of these changes can trigger an imbalance – or ‘dysbiosis’ – of the gut microbiota.2,9–11

Gut microbial dysbiosis is characterised by a loss of beneficial microbial organisms, e.g. bifidobacteria, and an expansion of potentially pathogenic bacteria.12

As 70-80% of immune cells are located in the gut, the immune system development relies on establishing a balanced and diverse gut microbiota in early life13,14; well developed gut microbiota populations are associated with improved health later in life, including reduced risk of allergies and persistence of allergic diseases.14

Our gastrointestinal tract contains up to 80% of our immune cells and 100 trillion gut microorganisms13–15

There are consistent associations between reduced infant intestinal biodiversity and allergic diseases. Infants with cow’s milk allergy or multiple food allergies have been shown to have gut microbiota dysbiosis, which may continue even after allergic symptoms have resolved.16–19

Exposure to antigens early in life

Antigens, including allergens, are substances that enter the body and trigger an immune response. The immune system needs to learn to recognise which substances are beneficial, such as foods, and which are harmful, such as certain bacteria. Based on this identification and assessment, the immune system develops a mechanism that allows it to tolerate certain antigens or clear other antigens. The first time the body encounters a new antigen, it will take days before the immune response is complete.

Tolerating the nutritional components of food is an active response by the immune system.

As the immune system has now learned that this substance could be harmful, it will be much quicker to respond when next exposed to the same antigen. This is the basis of our adaptive immune function. Reduced exposure to antigens in early life, and therefore a failure to educate the immune system appropriately, is another major contributing factor to the rise in allergy.10,20,21

Conversely, early exposure to antigens (including those arising from a diverse microbiota) is central to the development of a trained immune system, which in turn is an important factor in the prevention of allergies.

1.
Prescott, S.L., Origins: Early-life solutions to the modern health crisis. 2015: University of Western Australia Press, Crawly, Western Australia.
2.
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Pawankar R, et al. World Allergy Organisation (WAO): White book on allergy. Wisconsin: World Allergy Organisation, 2011.
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9.
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10.
Azad MD, et al. Impact of material intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG.2015.
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Haahtela T, Holgate S, Pawankar R, Akdis CA, Benjaponpitak S, CaraballoL, et al. The biodiversity hypothesis and allergic disease: world allergy organization position statement. World Allergy Organization Journal. 2013;6(1):3.
12.
Weizman Z. Dysbiosis – the concept of dysfunctional intestinal microbiota. In: Intestinal Microbiota Probiotics and Prebiotics: Comprehensive Textbook for Health Professionals, R. Orel (ed); Ljubljana Institute for Probiotics and Functional Foods, 2014.
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Vighi G, et al. Allergy and the gastrointestinal system. Clinical and Experimental Immunology, 153 (Suppl. 1): 3–6.
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West CE et al. J Allergy Clin Immunol. 2015;135:3-13.        .
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Mitsuoka T. Nutr Rev 1992;50:438-446.
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Penders J, Gerhold K, Stobberingh EE, et al. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013;132:601-607.e8.
17.
Bisgaard H, Li N, Bonnelykke K, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol. 2011;128:646-52.e1-5.
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Storro O, Avershina E, Rudi K. Diversity of intestinal microbiota in infancy and the risk of allergic disease in childhood. Curr Opin Allergy Clin Immunol. 2013;13:257-62.
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Bisgaard H, Bonnelykke K, Stokholm J. Immune-mediated diseases and microbial exposure in early life. Clin Exp Allergy. 2014;44:475-81.
20.
Brooks et al, 2013;
21.
Kramer et al, 2013 and Azad, 2015.