Summary
In which we explore the mechanisms underlying food allergy and intolerance. We start by asking why food allergies are not more common than they are and how the gut maintains a tolerance to ingested proteins. We then begin to dissect the layers of gastro-archeology, by examining the superficial layers of most recently evolved mechanisms. Here we find specialised IgE type antibodies against food that lead to familiar allergic responses through the release of chemicals such as histamine. However, on deeper excavation we find that allergic type responses can be generated even in the absence of T and B cells, whose responses are regulated by innate lymphoid cells. Digging lower and further back in time we see how the epithelium itself and bacteria in the gut may affect allergic responses and how modern food preparation may contribute. We consider desensitisation approaches and the drawbacks of oral vaccination. Finally, we discuss food intolerances as possible ‘partial’ food allergies that lack all of the layers of the complete response.
From ‘De Rerum Natura’ (= ‘on the nature of things’) by the Roman poet and philosopher known as Lucretius (98-55 BC), his only remaining work. From the Epicurean school of thought, Lucretius promulgated materialism in opposition to spiritualism. It contains one of the first suggestions of the existence of food allergy in historical literature.
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Helen Keller (1880–1968) became blind and deaf following a childhood illness—probably meningitis—at the age of 19 months. With the help of her tutor and subsequent companion of 49 years Anne Sullivan, she learnt the names for objects by feeling them in one hand whilst their names were spelt on the palm of the other. She was able to ‘lip read’ by touching people’s mouths as they spoke and to listen to music through a resonant table top. She became a renowned speaker and writer and an active champion for the rights of sensory disabled people.
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The alternative medicine branch of ‘Homeopathy was invented by Samuel Hahnemann (1755—1843) in his book ‘Organon of the healing art” in 1810. He was apparently convinced by the ancient idea of ‘similia similibus curentor’ (like cures like) by suffering malaria like symptoms when taking the then (and current) cure—cinchona bark, which contains quinine. The basic premise is that substances thought to be associated with a condition are diluted and the homeopath believes that they become more efficacious as a cure the higher the dilution. The art originally also required ‘succussing’ the solution or tapping the container vigorously on an elastic surface. The ‘centesimal’ scale represents a 100-fold dilution, hence a 2C dilution is a substance diluted 10,000 (100 x 100) times. It can easily be estimated that most preparations will not contain a single molecule of the supposed active substance—a dilution of 13C would be the equivalent of one drop in all the water on earth, and 40C would provide the equivalent of one molecule in all the molecules present in the entire known universe! Homeopathic remedies were sold at dilutions of up to 200C….! However not all homeopathic remedies were diluted to such an extent—one was sold at a 1/10 concentration and was sufficient to cause toxic side effects. Numerous scientific trials have failed to demonstrate any benefits of homeopathy beyond placebo and it has been recognised as ineffective and potentially harmful (through occasional toxicity, but also harmful misleading of vulnerable patients away from more effective remedies). Astonishingly this branch of ‘nonsense’ medicine (as it was described by the UK government Chief Scientific Adviser in 2013) was still supported and provided by the UK’s National Health Service until as recently as 2017.
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Immunoglobulin G antibodies to food are very commonly found in the blood stream in humans but their clinical relevance is questionable. The presence of IgG antibodies shows that some food proteins can get into the blood stream across the gut where an immune response can be generated and it is likely that their presence merely represents exposure to the protein but does not have any significance in causing symptoms. As is often the case, assumptions are made and put into commercial practice despite the lack of scientific evidence. There are companies that sell IgG antibody blood tests against food, claiming that they can guide elimination diets to treat a variety of different conditions or symptoms. Antibodies to cow’s milk protein and wheat are commonly found in most individuals, and these two foods are also commonly implicated in abdominal symptoms for reasons not associated with the immune system. Therefore, any benefit to individuals in excluding these foods is unlikely to be related to the detection of IgG antibodies in their blood. This is perhaps a case of ‘cause’ and ‘association’ being conflated at the cost of the unwitting for commercial gain.
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‘The strange case of Dr Jeckyll and Mr Hyde’ was a novella written by Robert Louis Stevenson in 1886 whilst convalescing from illness in Bournemouth. In the story, the benign Dr. Henry Jeckyll becomes increasingly unable to prevent his transformation into his murderous alter ego, Mr. Edward Hyde, despite concocting a potion that initially works to good effect, and takes his own life. The character is thought to be based on Stevenson’s friend Eugene Chantrelle, a French teacher in Edinburgh who murdered his own wife by poisoning her.
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HMGB1 stands for ‘High Mobility Group Box −1’ protein. I do not feel the need to explain why as it is not a particularly interesting explanation! However, the key chemical signals involved in signalling from the epithelial cells are called interleukin 33 (which is related to interleukin 1), thymic stromal lympho-poeitin (or TSLP) and interleukin 25 (secreted by the tuft cells). Interleukin 33 in particular is relevant as it is produced as a result of HMGB1 activating the RAGE receptors, and is shortened by the action of proteases to its active form.
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Actually (as purists will be keen to point out), there are 12. They are still numbered Ara h 1–11 as the 12th is called Ara h 3b
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The word ‘adjuvant’ derives from the latin verb adiuvare, meaning ‘to help’. It is of different derivation from ‘adjunct’ which comes from the verb adjungere, meaning ‘to add on’ or ‘join’.
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Woodward, J. (2021). What Is Food to One Is Rank Poison to another’. In: The Gastro-Archeologist. Springer, Cham. https://doi.org/10.1007/978-3-030-62621-1_7
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