Food allergies are a common reason for individuals to seek nutritional support and they appear to be becoming more prevalent in today’s society, with six to eight percent of children now affected worldwide.1 The prevention of allergy developing in infancy has been a major concern of healthcare professionals and government advice has sometimes appeared conflicting to parents. The main reason for this is that we are still only just understanding the processes by which allergies develop. Today’s blog discusses research into the causes of food allergies, as well as interventions to help support a healthy immune response to reduce the risk of allergies developing.
This blog mainly focuses mainly on food allergy mediated by IgE antibodies and which can potentially lead to anaphylaxis, other symptoms include swelling, oedema, skin rashes and nausea. However, it is also important to mention that many people may experience food sensitivities or intolerances (which are briefly discussed below) – while these can have a significant effect on health and wellbeing they are not life-threatening from the perspective of inducing anaphylaxis. Food sensitivities tend to be mediated by IgG antibodies and symptoms tend to be less immediate and include digestive problems and fatigue.
Mechanism of allergy
One of the main ways by which a food allergy is defined is that it is mostly mediated by the antibody IgE, produced by mast cells and basophils, which elicits an immune cascade response. This immune response is rapid; the onset of symptoms typically occurs within 5 to 60 minutes (although it can be more immediate) after exposure to the food.2
In a previously sensitised person with a food-specific IgE allergy, the food allergen is ingested and absorbed into the local tissue and then triggers the immediate release of preformed mediators as well as de novo synthesis of many inflammatory mediators such as certain leukotrienes, prostaglandins, and cytokines. This response can be considered life threatening in some circumstances as it can lead to anaphylaxis which involves multiple organ systems but most dangerously can lead to hypotension, respiratory collapse and potentially death if immediate intervention is not available.3
In many people food allergy is less dramatic and can often be observed as cutaneous manifestations such as hives and pruritus. However these skin conditions are absent in 20% of patients with anaphylaxis therefore suspicion of IgE mediated allergy is also considered when respiratory and digestive signs and symptoms such as cough, wheezing, laryngeal oedema, vomiting and diarrhoea, in addition to hypotension, are present.
Most food allergies present in infancy with some disappearing in late childhood or adulthood, although peanut allergies appear to be the most persistent and are often a lifelong condition. Allergies can also manifest later in life and are associated with a disturbance of the gut flora and epithelial barrier integrity.
Aetiology
It is still not fully understood how allergies manifest, there is clearly immune dysregulation which is also strongly associated with digestive health. For a long time it was considered that over exposure to a potential allergen had the ability to induce allergy. However, recent research seems to contradict this argument. Research in mouse models has identified mechanisms by which allergy seems to be induced.
Skin transmission
Epidemiologic data suggest that sensitisation to peanut protein can occur in children through the exposure to peanut in oils via inflamed skin, while early oral exposure to food antigen induces tolerance.
Food allergen consumption at home correlates with the incidence of food allergy. Furthermore, loss of function mutations in filaggrin, a gene that encodes the skin epithelial barrier protein filaggrin, conferred increased risk for atopic dermatitis (AD) and other allergies, including peanut allergy. These observations led to the hypothesis that the altered barrier function in AD skin may facilitate cutaneous sensitisation to food antigens, potentially leading to the development of food allergies.4
A recent study has shown that scratching the skin is associated with an increased number of activated mast cells within the small intestine. Further supporting the evidence that skin inflammation is associated with immune activity of the gut and may be contributory to the development of food allergy. It was demonstrated that scratching actives the cytokine IL-33, this then enters the blood stream. When IL-33 reaches the digestive system it works with IL-25, a protein secreted by cells in the lining of the intestine, which in turn activates ‘type 2 innate lymphoid cells’ (ILC2s). Activated ILC2s make two additional cell-signalling proteins, IL-13 and IL-4, which were found to be responsible for the increased number of intestinal mast cells.5
Maternal transmission
Studies in mice have demonstrated that antigen exposure during pregnancy and breast-feeding protected the offspring from allergic sensitisation. Transmission of TGF-β (transforming growth factor beta – a protein involved in epithelial development) and antigen or antigen-IgG immune complexes, via breast milk, was shown to induce this tolerance. The exposure of pregnant mothers to live bacteria was additionally demonstrated to prevent allergic phenotypes in offspring, implying protective effects by early-life microbial exposure.4
Reduced stomach acid
Stomach acid is essential for the normal breakdown of dietary proteins, the acid begins to chemically break hydrogen bonds (these bonds maintain proteins in a folded configuration) and also activates the proteolytic enzyme pepsin. Therefore, if there is inadequate stomach acid production protein digestion will be impaired and undigested proteins or large peptides may be antigenic, particularly coupled with leaky gut.
Studies have shown a correlation between reduced gastric output and food allergy. Patients taking acid-supressing medication have been shown to be at increased risk of developing food allergen sensitisation. Anti-ulcer medication during pregnancy has been associated with a higher risk of developing asthma in childhood. In vivo studies with pregnant mice have also shown that antacid treatment promoted oral sensitisation and IgE and Th2 hypersensitivity to hazelnut allergens in their offspring.4
Th2 Dominance
It is well documented that the balance of T-helper lymphocytes is essential for health. T-helper 1 lymphocytes (Th1) are responsible for inducing cell mediated immunity (e.g activation of phagocytes) and T-helper 2 lymphocytes (Th2) for inducing humoral immunity (e.g. antibody activation). It is essential that Th1 and Th2 are equally expressed (or supressed) in order to maintain a homeostatic immune system, excess Th1 is associated with tissue specific autoimmunity, excess Th2 is associated with allergy and atopy.
The neonatal immune system is biased towards Th2 dominance. Research suggests that an infant’s innate immune system requires a certain level of inoculation by dietary allergens to become fully competent and to balance the expression of Th1 and Th2 cytokines. This requirement for inoculation has led to the hygiene hypothesis.6,7
Hygiene Hypothesis
The gut microflora undoubtedly play a role in the protection against the development of allergies. The hygiene hypothesis has been well documented and supported by the strong correlation between low bacterial diversity and the risk of atopic and allergic conditions. Children who are exposed to a bacterially diverse environment during early development e.g. children who grow up on farms, with bacterial exposure from dust, animals, soil and siblings, have been shown to have a much reduced risk of allergy compared to children who are brought up in a cleaner, more sterile environment.
Environmental and lifestyle factors including obesity and lack of physical exercise, a diet rich in industrially processed foods, growing up as singlet in an urban home with an overall reduced microbial diversity and possibly exposure to antibiotics, are all associated with a decreased diversity of environmental microbes and a more or less pronounced gut dysbiosis. This, in turn, leads to an altered set-point of the innate immune system in early childhood, which facilitates loss of peripheral tolerance and the development of hypersensitivity later in life.6
Oral tolerance
Recent studies have shown that the introduction of eggs and peanuts in early childhood builds oral tolerance to these foods. However it appears there is a narrow time period where this type of introduction is successful; the window of opportunity for intervention is starting to close by the time the milestone of sitting is reached and is almost entirely closed upon reaching the milestone of walking.1
Gut flora
When a child is exposed to a non-sterile environment it is known that, as well as exposure to dietary allergens, the gut is also becoming inoculated with bacteria which play an essential role in immune development. Environmental factors, including a low-fibre/high-fat diet, caesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. Research into the microflora in the gut and food allergy onset has shown that: 8
- Dysbiosis precedes food allergy onset
- Microbial community structure early in life, particularly in the first six months of life, is more relevant in food allergy development
- Dysbiosis could influence not only the occurrence, but also the disease-course of food allergy. As suggested by different gut microbiota features comparing children who outgrow food allergy with patients with persistent food allergy
- Butyrate, a short chain fatty acid produced by healthy gut bacteria, which provides fuel for enterocytes in the colon, has been seen to be deficient in allergic children
- Maternal consumption of live bacteria supplements during pregnancy and breast-feeding, as well as in infants, is associated with a reduction in food allergy onset
Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory influenced behaviours.
Evidence suggests that specific healthy infant microbiome signatures may decrease atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.9
Leaky gut
The integrity of the digestive lining also plays a significant role in the onset of food allergy. The gut integrity of infants is often reduced and it has been shown that gastrointestinal permeability is increased in children with food allergies. Gastrointestinal epithelial dysfunction has been thought to contribute to food hypersensitivity through both increased sensitisation due to a leaky barrier and the heightened Th2 response that ensues.10
As well as being indicated in the onset of allergies in children, leaky gut is also consistent with food sensitivities later in life. If the epithelial barrier is compromised, larger dietary proteins can pass across the digestive lining, eliciting an immune response; this can also occur later in life. Sensitivities are mostly mediated by IgG antigens and do not tend to lead to anaphylaxis. Symptoms can also be more vague than with allergy but are often associated with skin and digestive system issues. Individuals who appear to react to many different foods, especially if symptoms are increasing over time, are likely to have gastrointestinal permeability.7,11
Histamine
Histamine is a molecule which is released during an allergic response and can lead to symptoms such as oedema, itchy, watery eyes as well as potentially anaphylaxis. Some foods are particularly high in naturally occurring histamine and can create a similar response in people who are sensitive to these foods. This is not necessarily an allergic response but more as a result of a high intake of histamine, coupled with a compromised ability to break-down histamine, which results in similar symptoms.12 Foods high in histamine include: wine, beer, alcohol, and champagne, fermented soy products (such as tempeh, miso, soy sauce, and natto), fermented grains (such as sourdough bread), tomatoes, aubergine and spinach.
Nutritional interventions
Once an allergy has developed it can be difficult to overcome. However supporting digestive health is important for prevention and as an intervention for food allergy and intolerance *(see note below).
Support a healthy bowel flora by:
- Eating prebiotic foods (providing fibre which is a fuel for gut bacteria) and polyphenols from chicory, olives, green leafy vegetables, baked apples with skin, onion, garlic and Jerusalem artichoke.
- Taking a live bacteria supplement and/or prebiotic (inulin, FOS, apple pectin) supplement
- Eating fermented foods such as kefir, kombucha, sauerkraut and miso
Consider the need for additional nutrients which aid the repair and integrity of the digestive lining such as:
- Vitamin A
- Vitamin D3
- L-Glutamine
- Zinc
- Lactoferrin
- Marshmallow root
Other nutrients which have been shown to modulate Th2 dominance may also be useful these include quercetin and spirulina.
- Quercetin has been shown improve the Th1/Th2 balance, and reduce antigen-specific IgE antibody formation13
- A study with allergic rhinitis patients demonstrated that spirulina can modulate the Th cell profile by suppressing the differentiation of Th2 cells14
*Please note: Some of these recommendations are not suitable for pregnancy. Check with a health practitioner. Regardless of nutritional interventions, reintroducing foods which trigger allergic symptoms should not be attempted unless under medical supervision. The advice provided here is for information only and should not be regarded as medical advice. Please always seek advice from your G.P. if food allergy is suspected.
Key Takeaways
- Food allergies mainly occur in children and can often be “out grown” as the child ages. However some allergies are persistent or can start later in life.
- The cause of food allergies is largely unknown but there is evidence to show that disruption to the gut integrity and gut microflora, leading to immune dysregulation, is involved.
- Maternal and infant exposure to potential allergens has been shown to improve oral tolerance and has potential to be a preventative strategy for food allergy. Current studies recommend low exposure to allergens such as eggs and peanuts at weaning.
- Exposure of inflamed or broken skin (such as eczema) to topical allergens has been shown to induce food allergy.
- Reduced levels of stomach acid and antacid medications are correlated with an increase in food allergy incidence, demonstrating the importance of the role of stomach function.
- Children who are brought up in an excessively sterile environment have a much higher risk of food allergy than children who are exposed to environments which contain bacteria and allergens such as pets, siblings and countryside etc. Inoculation of the gut in the early years with bacteria as well as exposure to allergens helps to support the competence and balance of the immune system. (On the other hand, this is not to say that poor hygiene is recommended, as this can lead to other problems).
- Support digestive function with interventions such as live bacteria, prebiotics and nutrients to support gut integrity, which is often compromised when intolerances are present.
Relevant Cytoplan products
Cytoprotect GI Tract – a synergistic multi-nutrient, botanical and live bacteria formula designed to support the integrity and stability of the mucosal barrier membranes of the entire gastrointestinal tract. It contains vitamin A, vitamin D, copper, zinc, slippery elm, marshmallow root powder, apple pectin, lactoferrin, quercetin and Bacillus coagulans. This product is designed for short-term use under the guidance of a health practitioner.
Acidophilus Plus – live bacteria supplement including 9 strains as well as FOS. Suitable for pregnancy.
Alternative products Fos-A-Dophilus, Cytobiotic Active, Sacharmoyces Boulardii
Phytoshield – phytonutrient complex containing flavonoids and carotenoids including quercetin.
Organic Spirulina – 1 tablet provides 500mg
L-Glutamine – 1 tsp provides 5g of L-glutamine
Organic Turmeric Plus – curcumin, gotu kola and cat’s claw
NB: Some of these products are not suitable for pregnancy. Check with a health practitioner.
References
- Du Toit G, Foong R-X, Lack G (2016) ‘Prevention of food allergy – Early dietary interventions’, Allergol Int, 65(4) pp370-377.
- Solomon CG, Jones SM, Burks AW (2017) ‘Clinical Practice Food Allergy’, n engl j med 12 pp1168-1176.
- Yu W, Freeland DMH, Nadeau KC (2016) ‘Food allergy: immune mechanisms, diagnosis and immunotherapy’, Nat Rev Immunol, 16(12) pp751.
- Oyoshi MK, Oettgen HC, Chatila TA, Geha RS, Bryce PJ. (2014) ‘Food allergy: Insights into etiology, prevention, and treatment provided by murine models’, J Allergy Clin Immunol, 133(2) pp309-317.
- Leyva-Castillo J-M, Galand C, Kam C, et al. (2019) ‘Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion’, Immunity, 0(0).
- Gilles S, Akdis C, Lauener R, et al (2018) ‘The role of environmental factors in allergy: A critical reappraisal’, Exp Dermatol, 27(11) pp1193-1200.
- Bland J et al. Textbook of Functional Medicine.; 2008.
- Berni Canani R, Paparo L, Nocerino R, et al. (2019) ‘Gut Microbiome as Target for Innovative Strategies Against Food Allergy’, Front Immunol, 10:191.
- Chernikova D, Yuan I, Shaker M. (2019) ‘Prevention of allergy with diverse and healthy microbiota’, Curr Opin Pediatr, April 2019:1.
- Vickery BP, Scurlock AM, Jones SM, Burks AW. (2011) ‘Mechanisms of immune tolerance relevant to food allergy’, J Allergy Clin Immunol, 127(3) pp576-84-6.
- Choung RS, Talley NJ. Food Allergy and Intolerance in IBS. Gastroenterol Hepatol (N Y). 2006;2(10):756-760. http://www.ncbi.nlm.nih.gov/pubmed/28325993. Accessed April 15, 2019.
- Pinzer TC, Tietz E, Waldmann E, Schink M, Neurath MF, Zopf Y. (2018) ‘Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls’, Allergy, 73(4) pp949.
- Mlcek J, Jurikova T, Skrovankova S, Sochor J. (2016) ‘Quercetin and Its Anti-Allergic Immune Response’, Molecules, 21(5).
- Sayin I, Cingi C, Oghan F, Baykal B, Ulusoy S. (2013) ‘Complementary Therapies in Allergic Rhinitis’, ISRN Allergy, 2013:938751.
Last updated on 20th October 2022 by cytoffice
Very informative article. Thank you
What are the food that are not consumable
I’m afraid I don’t understand your query – please email our team of nutritional therapists on nutrition@cytoplan.co.uk and we will be able to pick this up further.