Researchers from the University of British Columbia have shown for the first time how and why antibiotic depletion of microbes in the gut of newborns can lead to lifelong respiratory allergies.
This is evident from a study published today in the 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 many new avenues for exploring possible preventions and treatments.
“Our research finally shows how gut bacteria and antibiotics shape a newborn’s immune system, making them more susceptible to allergies,” said senior author Dr. Kelly McNagny. (he/him)professor at 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-established path that could have lasting consequences for susceptibility to chronic disease as an adult.”
Allergies are a result of the immune system overreacting to harmless substances such as pollen or pet dander, and a leading cause of emergency room visits in children. Normally, the immune system protects us against harmful invaders such as bacteria, viruses and parasites. In the case of 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 phase for the development of our immune system starts very early in life. Research over the past twenty years has shown that microbes in the intestines of young children play a key role. Babies are often given antibiotics soon after birth to fight infections, and these can reduce certain bacteria. Some of those bacteria produce a compound called butyrate, which is crucial for stopping the processes uncovered in this study.
Dr.’s laboratory McNagny had previously shown that babies 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 at an early age.
By studying the process in mice, they have now discovered how this works.
Mice with depleted gut bacteria that were not given a butyrate supplement developed twice as many of a certain type of immune cell called ILC2s. Discovered less than 15 years ago, these cells have quickly become prime suspects in the development of allergies. The researchers showed that ILC2s produce molecules that ‘flip a switch’ on white blood cells, causing them to produce an abundance of certain types of antibodies. These antibodies then 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 silencing them.
Butyrate must be given within a limited period of time after birth – a few months for humans, a few weeks for mice – to prevent the proliferation of ILC2s and all that follows. If that opportunity is missed and the ILC2s multiply, the remaining steps are assured and stay with someone for life.
Now that researchers know what those other steps are, they have many more potential targets to halt the cascade even after the supplementation window closes.
“We can now detect when a patient is about to develop lifelong allergies simply by the increase in ILC2s,” says Ahmed Kabil (he/him), the first author of the study and a PhD candidate at the SBME. “And we may be able to target those cell types instead of relying on butyrate supplementation, which only works at a young age.”
Like Dr. McNagny and co-research leader Dr. Michael Hughes notes, treating people’s allergies with antihistamines and inhalers relieves symptoms but does not cure the disease. To make more sustainable progress, researchers must focus on the cells and mechanisms that build this hypersensitive immune system. Until now there was no selective way to do that.
With this new insight, patients can look forward to more effective long-term solutions that address the root cause of the problem and pave the way to a future where allergies are managed more effectively or perhaps even avoided altogether.
