Researchers at the University of British Columbia have shown for the first time how and why the destruction of microbes in a newborn’s gut by antibiotics can lead to lifelong respiratory allergies.

In a study published today in Journal of Allergy and Clinical ImmunologyA research team from the School of Biomedical Engineering (SBME) has identified a specific cascade of events that lead to allergies and asthma, opening up many new avenues for research into potential prevention and treatment options.

“Our research finally shows how gut bacteria and antibiotics affect a newborn’s immune system, making them more susceptible to allergies,” said lead author Kelly McNagny, Ph.D., professor in the SBME and the Department of Medical Genetics.

“When you see something like this, it really changes the way you think about chronic disease. This is a well-developed pathway that can have lasting effects on susceptibility to chronic disease in adulthood.”

Allergies are the result of the immune system overreacting to harmless substances such as pollen or animal dander, and are a major reason for children to visit the emergency room. Normally, the immune system protects us from harmful invaders such as bacteria, viruses and parasites. In allergies, it mistakes something harmless for a threat – in this case, parasites – and triggers a reaction that causes symptoms such as sneezing, itching or swelling.

The course for the development of our immune systems is set very early in life. Research over the past two decades has shown that microbes in the infant gut play a key role. Babies are often given antibiotics shortly after birth to fight infections, and these can reduce certain bacteria. Some of these bacteria produce a compound called butyrate, which is crucial in stopping the processes uncovered in this research.

Dr. McNagny’s lab had previously shown that infants with fewer butyrate-producing bacteria were particularly susceptible to allergies. They had also shown that this could be mitigated or even reversed by giving butyrate as a dietary supplement early in life.

By studying the process in mice, they have now discovered how it works.

Mice with depleted gut flora that did not receive a butyrate supplement developed twice as many immune cells of a specific type called ILC2. These cells, discovered less than 15 years ago, are quickly becoming the prime suspects in the development of allergies.

The researchers showed that ILC2s produce molecules that flip a switch in white blood cells so that they produce large quantities of certain antibodies. These antibodies then coat the cells as a defense against foreign invaders, giving the allergic person an immune system that is ready to attack at the slightest provocation.

The number of all cells, molecules and antibodies along this cascade increases dramatically if they are not suppressed by butyrate.

Butyrate must be administered within a narrow window of time after birth – a few months in humans, a few weeks in mice – to prevent the proliferation of ILC2s and everything that follows. If this opportunity is missed and ILC2s proliferate, the remaining steps are assured and will remain with the patient for life.

Now that researchers know what the next steps are, they have many more potential targets to stop the cascade, even after the window for supplementation has closed.

“We can now tell when a patient is on the verge of developing lifelong allergies simply by the increase in ILC2s,” said Ahmed Kabil (he/him), first author of the study and a doctoral student in the SBME. “And we can potentially target these cell types rather than relying on butyrate supplementation, which only works at a young age.”

As Dr. McNagny and study co-leader Dr. Michael Hughes point out, treating allergies with antihistamines and inhalers relieves symptoms but does not cure the disease. To make more sustainable progress, researchers need to target the cells and mechanisms that build this oversensitive immune system. Until now, there has been no targeted way to do this.

With this new understanding, patients can look forward to more effective, long-term solutions that address the root of the problem, paving the way for a future where allergies can be more effectively treated or perhaps even prevented altogether.