Scientists explore the causal role of gut microbiota in food allergy

Rates of food allergy in children are spiking and it’s not certain why this increase in prevalence has occurred. The gut microbiome could play a role.

Peanut butter, milk, and bread: they’re all classic staples of childhood. They’re also the foods that more and more kids’ bodies identify as strange and harmful substances, in some cases initiating a life-threatening anaphylactic reaction.

Rates of food allergy in infants and children are spiking in many areas of the world, with milk, eggs, soy, wheat, and peanuts being some of the most common offenders. It’s not certain why this increase in prevalence has occurred—but it makes the scientific study of food allergy prevention and treatment ever more important. And the latest research indicates that the gut microbiome of infants and children could play a part in how food allergy ends up developing.

Food allergy is characterized by an adverse health effect upon exposure to a specific food, or ‘antigen’. In the most common form of the condition, so-called ‘IgE-mediated allergy’, a very specific immune response occurs: the antigen activates immune cells called Th2 cells, which spur the production of antibodies belonging to a class called immunoglobulin E (IgE) and set them loose in the bloodstream. This triggers symptoms, ranging from a skin rash to a severe, whole-body anaphylactic reaction.

Cow’s milk allergy is of particular interest because in the first months of life, babies have to drink milk of one kind or another, with cow’s milk being a common alternative to breast milk. It’s been observed that children with cow’s milk allergy have pronounced differences in their gut microbiota compared with healthy children; and one study showed differences in gut microbiota composition of infants at 3-6 months whose milk allergy ended up resolving by the age of eight.

A humanized mouse study from the laboratory of Cathryn Nagler of University of Chicago (USA) took this work a step further, exploring whether the gut microbiota could have a causal role in allergic reactions to foods. First, the researchers took fecal samples from a small group of infants who were healthy and a small group who had confirmed IgE-mediated cow’s milk allergy, and confirmed the existence of significantly different bacterial communities.

Then came the mouse experiment: germ-free mice were ‘sensitized’ (made allergic) to a cow’s milk component before being colonized with the gut microbes of the healthy infants and those with cow’s milk allergy.

When the mice were exposed to the antigen, researchers saw an anaphylaxis reaction and a more pronounced immune response in the ones colonized with microbiota from allergic infants; and the mice that had received a healthy infant’s microbiota were protected from the anaphylactic response.

The researchers then took a closer look, correlating various bacterial species with genes that were upregulated in the mice who experienced or didn’t experience anaphylaxis; they identified a bacterial species that appeared to be protective against allergic responses: Anaerostipes caccae. Sure enough, if germ-free mice were colonized only with this species they did not experience anaphylaxis when they encountered the cow’s milk antigen.

A more recent mouse study provided further evidence for the potential ‘calming’ effect of the early life gut microbiota on immune responses related to food allergy. Researchers were exploring a known phenomenon: young germ-free mice that after weaning start to eat normal foods, typically experience an allergy-linked immune response. Korean and Australian researchers found that this response happens along with a spike in T follicular helper (TFH) cells—which are typically generated in early life but are dampened when a gut microbiota is present. This work supports the existence of a food-allergy-protective microbiota in infancy, at a time when the immune system is rapidly developing.

All of this evidence contributes to the idea that the gut microbiota could play an active role in food allergy and how it emerges in early life. But what about kids who already deal with food allergy—is there any hope to mitigate it?

Some microbiome-focused treatments are already under investigation: for instance, one trial found that peanut oral immunotherapy plus a specific probiotic (Lactobacillus rhamnosus CGMCC 1.3724) was effective for inducing immune changes and unresponsiveness to a peanut protein in children with established peanut allergy.

Further research from different angles and in different models should help uncover the role of the gut microbiota in the immune responses involved in food allergy—with the hope that microbiota manipulation could soon help more children enjoy a peanut butter sandwich without consequence.

Kristina Campbell