Researchers at the University of British Columbia have shown for the first time how and why the reduction of microbes in a newborn’s gut by antibiotics can lead to lifelong respiratory allergies.
In a study published today in the journal 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. In doing so, they have opened up many new avenues for exploring potential preventions and treatments.
“Our research finally shows how gut bacteria and antibiotics shape a newborn’s immune system to make it more prone to allergies,” said lead author Dr. Kelly McNagny. (he/him)professor at 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-designed pathway that can have long-lasting consequences on susceptibility to chronic disease in later life.”
Allergies result from the immune system reacting too strongly to harmless substances like pollen or pet dander, and are a leading cause of emergency room visits in children. Normally, the immune system protects us from harmful invaders like bacteria, viruses, and parasites. In the case of allergies, it mistakes something harmless for a threat (in this case, parasites) and triggers a response that causes symptoms like sneezing, itching, or swelling.
The development of our immune system is established very early in life. Research over the past two decades has pointed to microbes in a baby’s gut as playing a key role. Babies are often given antibiotics soon after birth to fight infections, and these can reduce the activity of certain bacteria. Some of these bacteria produce a compound called butyrate, which is key to stopping the processes discovered in this research.
Dr. McNagny’s lab had previously shown that infants with fewer butyrate-producing bacteria become particularly susceptible to allergies. They had also shown that this could be mitigated or even reversed by providing butyrate as a supplement in the first few years of life.
Now, by studying the process in mice, they have discovered how it works.
Mice with reduced gut flora that were not given any butyrate supplements developed twice as many of a type of immune cell called ILC2s. These cells, discovered less than 15 years ago, have quickly become prime suspects in the development of allergies. Researchers showed that ILC2s produce molecules that “flip” a switch in white blood cells to make large numbers of certain types of antibodies. These antibodies coat the cells as a defense against foreign invaders, giving the allergic person an immune system ready to attack at the slightest provocation.
Every cell, molecule, and antibody described along this cascade increases dramatically in number without butyrate to reduce them.
Butyrate must be administered for a limited period of time after birth (a few months in humans and a few weeks in mice) to prevent the proliferation of ILC2s and all that entails. If that opportunity is missed and the ILC2s multiply, the remaining steps are assured and the person will remain with it for life.
Now that researchers know what those other steps are, they have many more potential targets to stop the cascade, even after the supplementation window has closed.
“We can now detect when a patient is about to develop lifelong allergies, simply by the increase in ILC2,” said Ahmed Kabil (He/him), first author of the study and a PhD candidate at SBME. “And we can potentially target those cell types rather than relying on butyrate supplementation, which only works in the early stages of life.”
As Dr. McNagny and co-director Dr. Michael Hughes point out, treating allergies with antihistamines and inhalers relieves symptoms but does not cure the disease. To make more lasting progress, researchers need to focus on the cells and mechanisms that build this hypersensitive immune system. Until now, there has been no selective way to do so.
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 are more effectively controlled or perhaps prevented altogether.