For reasons that remain a mystery, the number of Americans who suffer from food allergy has risen sharply over the last decade to as many 32 million, according to one recent estimate. Nearly 8% of american children (about two in every classroom) are affected. One hypothesis is that certain Western lifestyle factors — an increase in births by Caesarean section, a decline in breastfeeding, increased use of antibiotics and smaller family sizes, for example — is disrupting the normal microbial balance in the gut, depriving babies of the “good” bacteria that prepare the immune system to recognize food as harmless. But hypotheses are not lacking. Actually, this suspicion did stem at least 10 years ago, when th “microbiota” factor was becoming more and more interesting and apparently involved in a plethora fo human medical conditions, starting from autoimmunity and spannig from diabetes, to gut inflammatory diseases to reach carcinogenesis.
Tens of articles concerning microbiota are published in this website, either in english or italian. A fast search with “keyword” will satisfy all those curious about it. A study by scientists at Boston Children’s Hospital and Brigham and Women’s Hospital, published in 2019, claimed to have an answer, that the national epidemic of food allergy is caused by the absence of certain beneficial bacteria in the human gut. But the study, conducted primarily in mice, also points the way toward treatments that may protect children from developing food allergies — and reverse the disease in people who already have it. In other words, the loss of these bacteria acts as a switch that makes children susceptible to food allergy. The team began testing this hypothesis by studying gut bacteria in babies with and without food allergies. They collected stool samples from 56 food-allergic patients and 98 matched controls. Then they analyzed those samples for changes in bacterial content.
The work revealed that the bacteria in the feces of babies with food allergies were different from those of controls. But did those bacterial differences play a role in their food allergies? To find out, the team transplanted fecal bacteria from the babies into a special strain of allergy-prone mice. They fed the mice small doses of chicken egg protein to sensitize their immune systems to this allergen, then challenged the mice with a large dose. What they found is that mice that had been given fecal bacteria from food-allergic babies went into the life-threatening reaction called anaphylaxis; that is, fhe fecal bacteria from food-allergic subjects did not protect against food allergy, whereas the bacteria from control subjects did. This result has been replicated this year on true twins, one of which was allergic to foodstuff and the other was not. To find out which bacteria might be offering that protection, the team tested a mix of six bacterial species from the order Clostridiales, which previous studies had suggested might protect against food allergy.
When these bacteria were given to the mice, the animals were protected from food allergy to chicken egg protein, whereas mice given other common bacteria were not. Then they provided a second mix of unrelated bacteria from the order Bacteroidales. It too was protective. And finally, when the team treated mice that already had food allergy with the Clostridiales or Bacteroidales mixes, they found those therapies completely suppressed the animals’ allergic reactions. While previous studies have suggested that certain bacteria can protect against food allergies, the joint team a step further, describing the specific immunological pathway by which the bacteria act in mice. It begins with a protein called MyD88, that serves as a “molecular sensor” for bacteria in the immune system’s regulatory T cells. In simple words, you need the bacteria to give particular signals that are picked up by nascent regulatory T cells in the gut.
Those signals trigger a chain reaction that changes the gut regulatory T lymphocytes into a specific type, known as ROR-gamma LTs, that protect against food allergies. More recently, however, scientists delved more in collateral signaling mechanisms that might explain the tight relationship between microbiota composition and food allergy. There are claims that metabolites produced by bacteria themselves may drive the corrects sequence of events that keep the whole system in balance. Two of them are the short-chain fatty acids (SCFAs) propionic and butyric acids. SCFA’s can be produced by bacteria through fermentation of dietary fibers. Certain bacterial strains such as Bifidobacterium longum, Clostridia and Bacteroides fragilis can induce intestinal Treg cells that are able to suppress food allergy and colitis. SCFA’s are able to enhance dendritic cell regulatory activity, leading to the induction of Treg cells and IL-10-secreting T cells.
It was shown that infants with a diet consisting of high levels of fruits and vegetables is associated with less food allergy by the age of 2 years, which could be due to an increased amount of dietary fiber intake. Moreover, pattern-recognition receptor activation (TLR-MyD88) is a potential mechanism by which intestinal microbes (e.g. Lactobacillus rhamnosus and L. reuteri) may promote Treg cell differentiation. Another study showed that allergen-sensitized mice had a different microbial composition compared to wildtype mice with an increased abundance of different bacterial families including Lachnospiraceae, Lactobacillaceae, Rikenellaceae and Porphyromonas. This different microbial composition increased ovalbumin-specific responses and anaphylaxis when reconstituted in wild-type germ-free mice, which indicates that the microbial composition play a role in food allergy by the age of 2 years, which could be due to an increased amount of dietary fiber intake.
This inderscores the importance to start the dietary fibers introduction as early as the step that an infant is able to chow raw food or processed food enricherd wirh vegetal fibers. There are also proofs that nitrogen-bsed bacterial metabolites may play a role in the processa s well. Bacterial bioamines like histamine and indole derivatives (indoleamine, indolacetate, scatole, etc.) may regular airways responsiveness to certain allergenes. Food allergy, finally, could stem from changes in microbial exposure in early life, which affect host microbiota composition, modifies the development of host immunity, and causes pathogenic immune responses to food allergens. Good bacteria producing SCFA and promoting gut and immmune health are thos contained in fermented foods like kombucha, yogurt, kefir and the like. To strongly reduce the risk for a future predisposition to food allergies, thus, it is advisable to promote vegetal fibers introduction since childhood.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Lee KH, Guo J et al. Int J Mol Sci. 2021; 22(4):2079.
Bao R et al. J Clin Invest. 2021 Jan; 131(2):e141935.
Kreft L et al. Front Immunol. 2020 Aug 14; 11:1853.
Abdel-Gadir A et al. Nat Med 2019; 25(7):1164-74.
Satitsuksanoa P et a. Front Immunol. 2018; 9:2939.
Biswas A et al. Nat Commun. 2018 May 3; 9(1):1779.
Ai C et al. PLoS One. 2016 Oct 20; 11(10):e0164697.