Researchers have uncovered the mechanisms explaining how the loss of gut microbes in newborns due to antibiotics can result in long-lasting respiratory allergies. This team of researchers has pinpointed a distinct sequence of events that lead to allergies and asthma, paving the way for new potential preventive measures and treatments.
A team from the University of British Columbia has revealed for the first time how the reduction of microbes in a newborn’s gut caused by antibiotics can result in lifelong respiratory allergies.
Today, a study published in the Journal of Allergy and Clinical Immunology by researchers from the School of Biomedical Engineering (SBME) has clarified how specific processes lead to allergies and asthma. This breakthrough opens many paths for investigating possible prevention strategies and therapies.
“Our findings clarify how gut bacteria and antibiotics influence a newborn’s immune system, making them more susceptible to allergies,” explained the lead author Dr. Kelly McNagny (he/him), a professor in both the SBME and the medical genetics department. “This discovery alters our understanding of chronic illnesses. It highlights a well-defined pathway that may have enduring effects on the risk of chronic diseases in adulthood.”
Allergies occur when the immune system overreacts to innocuous substances such as pollen or pet dander, and they are a major reason for emergency room visits among children. Normally, our immune system defends against harmful pathogens like bacteria, viruses, and parasites. However, during allergic reactions, it mistakenly identifies harmless substances as threats—similar to how it would react to parasites—triggering symptoms like sneezing, itching, or swelling.
The groundwork for our immune system’s development is established quite early in life. Research conducted over the last 20 years indicates that gut microbes in infants play a crucial role. Newborns are often administered antibiotics shortly after birth to fight infections, which can reduce certain beneficial bacteria. Some of these bacteria produce butyrate, a compound significant for inhibiting the processes identified in this research.
The lab led by Dr. McNagny had previously demonstrated that infants lacking butyrate-producing bacteria are particularly vulnerable to allergies. They also found that this vulnerability could be countered or even reversed by administering butyrate as a supplement during infancy.
Now, by examining the process in mice, they have gained insights into how this works.
Mice that had reduced gut bacteria and did not receive butyrate supplements developed twofold more of a particular immune cell known as ILC2s. Discovered less than 15 years ago, ILC2s have quickly been implicated in allergy development. The researchers illustrated that ILC2s produce substances that activate white blood cells to generate large amounts of specific antibodies. These antibodies then coat cells as a defense against perceived threats, priming the allergic individual’s immune system to react aggressively at minimal stimuli.
Each cell, molecule, and antibody outlined in this process significantly increases in quantity when butyrate is absent.
Butyrate needs to be provided during a limited timeframe shortly after birth—months for humans and weeks for mice—to prevent the growth of ILC2s and all subsequent effects. Missing this critical opportunity and allowing ILC2s to multiply ensures that the chain of events will persist throughout life.
With a clearer understanding of these additional steps, researchers now have various new targets for interrupting the cascade of events, even after the early life supplementation period has passed.
“We can now identify when a person is about to develop long-lasting allergies by simply monitoring the increase in ILC2s,” remarked Ahmed Kabil (he/him), the first author of the study and a PhD candidate in the SBME. “This means we can potentially focus on those specific cell types rather than depending solely on butyrate supplements, which are effective only early in life.”
As Dr. McNagny and co-lead researcher Dr. Michael Hughes have emphasized, current treatments for allergies utilizing antihistamines and inhalers alleviate symptoms but do not cure the condition. To make meaningful advancements, researchers must concentrate on the cells and processes that create this hypersensitive immune response. Until now, no targeted approach existed.
Armed with this newfound knowledge, patients can anticipate more effective, sustainable solutions that tackle the root cause of allergies, setting the stage for a future where allergies can be managed more successfully, or possibly even prevented entirely.
