In the past, we’ve discussed the rise of food allergies and spike in hospitalizations for food-based anaphylaxis. There are numerous theories as to why this is happening, but research is increasingly pointing to changes in the gut microbiome.
This past January, Yale researchers published a perspective piece proposing the introduction of chemicals and processed foods to our diet, coupled with the rise of hygiene products and antibiotics, have disrupted our gut microbiome and the biological control mechanisms—quality control (QC) systems—that help regulate our immune system, and that these disruptions may explain the rise in food allergy frequency and severity.
The lead author of this paper, Dr. Ruslan Medzhitov, discussed his research with us recently regarding the connection between the gut microbiome and food allergies. This post expands on this link while presenting the researchers’ novel hypothesis on allergy origin theory.
FOOD ALLERGIES AS QUALITY CONTROL
Understanding a disease starts with understanding its origin. Many diseases are extreme or faulty versions of otherwise normal biological processes. Sepsis, for example, is an overreaction of the body’s normal immune response to infection. If we assume this is the case with allergies, what then is the normal biological function going awry? These researchers propose it may have something to do with our body’s QC systems.
To detect substances, our bodies generally use olfactory (smell), gustatory (taste), and gut receptors. When these receptors identify the presence of a dangerous food, the body triggers a wave of defense mechanisms, ranging from sensing a bad odor or taste, to more aggressive ones like vomiting and diarrhea.
Guilty by Association VS INTRINSIC HARM
One major challenge for our QC systems is that in recent decades, the number of chemicals in the foods we eat has grown considerably, which has made it difficult for QC systems to identify and discern all possible harmful substances. Some can also bypass detection completely. For example, arsenic is tasteless and odorless, and cyanide famously smells like almonds (for some people). In either case, the body won’t detect the danger until it’s already too late. One tool the body uses to manage this is “guilt by association”: it takes a substance it can detect—and that often accompanies something harmful—to alert you to the food’s risk. One example the paper gives is cadaverine, which is not inherently dangerous but produces the smell you associate with rotting meat.
According to the article, this link is key to understanding why peanut butter kills some but spares others.
To answer this, the authors found it helpful to split allergens into two types. The first type covers allergens like venoms and dust mite allergens, which are intrinsically harmful and can trigger an immune response on their own (they are called immunogens). The second type covers guilt-by-association allergens. These allergens can bind to antibodies, but generally aren’t inherently dangerous (e.g., peanuts) and are not immunogens. In order to trigger an immune response, the second type of allergen needs to be paired with an immunogen. Food allergens fall into the second category.
The hypothesis of this paper is the immunogen paired with a food allergen is a harmful substance that is in some way associated with the food allergen—in this way, when your body uses its guilt-by-association protocols, the result is a food allergy. This can happen because the allergen and the noxious substance are intrinsically connected in some way, or because they were coincidentally eaten at the same time, and now the body associates the food allergen with this substance. In fact, a study referenced by the paper showed in one instance, the allergenic protein alone did not trigger an allergic response, but when it was consumed alongside a cholera toxin, it became allergenic! No matter how this association happens, the allergen is now the target of the immune system, and a flood of antibodies will now go after this perceived invader.
The million-dollar question these researchers posed is this: What noxious substances are associated with common allergenic foods? The article offers some plausible contenders. For plant allergenic foods (e.g., soy and legumes), toxins that defend the plants against herbivores may be the culprits. For non-plant allergenic foods (e.g., milk and fish), viruses from the animal could be to blame. The effects of these associates are typically mild, causing only minor issues with digestion, metabolism, and irritation. But when they are paired with the allergen via guilt-by-association, the allergic response is an overreaction that can turn lethal.
And there you have it, some of the latest cutting-edge research on allergy origin theory! While this is one group’s hypothesis and not conclusive, it’s certainly a fascinating and potentially powerful explanation. We still have a long way to go to fully understand food allergies, and explorations like this are always a great way to reframe our thinking and help us move the needle of knowledge forward!
— Nazir and the Allergy Amulet Team
This article was reviewed by Dr. Ruslan Medzhitov for accuracy.
Dr. Ruslan Medzhitov is the Sterling Professor of Immunobiology at Yale University School of Medicine, a Howard Hughes Medical Institute investigator, and the Chief Science Officer of the Food Allergy and Science Initiative (FASI). His laboratory is focused on allergy, inflammation, infection biology, cell signaling, and transcriptional control of cell fate decisions.
Food Allergy Science Initiative (FASI) is a research network encompassing 20 world-class laboratories and over 100 scientists dedicated to unraveling the mysteries underlying food allergies at the cellular and molecular level. FASI employs a cross-disciplinary and collaborative approach for accelerating breakthrough discoveries poised to transform the lives of patients with food allergies. FASI is widely known for pioneering important new research discoveries in the food-gut-brain axis, and for uncovering a novel theory involving the role of the nervous system in food allergies—or neuroimmune communications.