UBC research pinpoints how early-life antibiotics turn immunity into allergy

Researchers at the University of British Columbia have shown for the first time how and why the depletion of microbes in a newborn's gut by antibiotics shapes their immune system to make them more prone to respiratory allergies. 

In a study published in the Journal of Allergy and Clinical Immunology, a research team from the School of Biomedical Engineering identified the cascade of events that lead to allergies and asthma. The stage for the immune system’s development is set very early in life, and microbes in the infant gut play a key role. Babies often receive antibiotics shortly after birth to combat infections, and these can diminish certain bacteria. Some of those bacteria produce a compound called butyrate, which is key to halting the processes uncovered in this research.

Dr Kelly McNagny, PhD, is the senior author and a professor in the Department of Medical Genetics and School of Biomedical Engineering. Dr McNagny’s lab had previously shown that infants with fewer butyrate-producing bacteria become particularly susceptible to allergies, and that this could be mitigated or reversed by providing butyrate as a supplement in early life. Now, by studying the process in mice, they have discovered how this works.

Mice with depleted gut bacteria who received no butyrate supplement developed twice as many of a certain type of immune cell called ILC2s. These cells have become prime suspects in allergy development. The researchers showed that ILC2s produce molecules that flip a switch on white blood cells to make them produce an abundance of certain kinds of antibodies. The antibodies then coat cells as a defense against foreign invaders, giving the allergic person an immune system that is ready to attack at the slightest provocation.

Every cell, molecule, and antibody described along this cascade increases dramatically in number without butyrate to dampen them. To prevent the proliferation of ILC2s and all that follows, butyrate must be given during a narrow window after birth—a few months for humans, a few weeks for mice. If that opportunity is missed and ILC2s multiply, then the remaining steps are assured and remain with somebody for life. Knowing what those other steps are, researchers now have many more potential targets for halting the cascade, even after the supplementation window has closed.

Treating people’s allergies with antihistamines and inhalers relieves the symptoms but does not cure the disease. To achieve more lasting progress, researchers must target the cells and mechanisms that build this hypersensitive immune system. 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 managed more effectively, or perhaps avoided altogether.
 

hidden

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.