Researchers at the University of British Columbia have demonstrated for the first time how and why depleting a newborn’s gut microbiota with antibiotics leads to lifelong respiratory allergies.
In a recently published study, a research team from the School of Biomedical Engineering (SBME) has identified a specific chain of events that leads to allergies and asthma. In doing so, they have opened up several new avenues for exploring potential prevention and treatment.
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 managed, or perhaps avoided altogether.
In a study published August 10 in the journal Allergy and Clinical Immunology, a research team from the School of Biomedical Engineering identified a chain of events that lead to allergies and asthma. With this discovery, they opened up new avenues for exploring prevention mechanisms and potential treatments.
“Our research finally shows how gut bacteria and antibiotics influence a newborn’s immune system, making them more susceptible to allergies,” said lead author Dr. Kelly McNagney, professor in the School of Biomedical Engineering and Department of Medical Genetics. “When you see something like this, it completely changes your understanding of chronic disease. It’s a finely regulated process that could have long-lasting effects on susceptibility to chronic disease in adulthood.”
Allergy and Immunology
Allergies are the result of the immune system overreacting to harmless substances, such as pollen or animal dander, and are a leading cause of emergency room visits for children. The immune system protects the body from harmful invaders, such as bacteria, viruses, and parasites. In an allergy, the immune system mistakes something harmless for a foreign threat, and then triggers a response that causes symptoms such as sneezing, itching, or swelling.
The immune system is formed very early in life, and research over the past two decades has suggested that the microbes in an infant’s gut play a key role.
What do bacteria do to protect the body from itself?
Babies often receive antibiotics soon after birth to fight infections, and these can reduce the number of certain types of bacteria. Some of these bacteria produce a compound called butyrate, which is key in stopping the processes uncovered in this research.
Dr. McNagney’s labs have previously shown that infants with fewer butyrate-producing bacteria are more susceptible to allergies. They have also shown that this can be mitigated or even reversed by supplementing with butyrate early in life.
Now, by studying this process in mice, they’ve discovered how it works.
Mice that had their gut bacteria depleted and did not receive the butyrate supplement developed a specific type of immune cell called type 2 innate lymphocytes in double numbers.
These cells were discovered less than 15 years ago, and quickly became a prime suspect in the development of allergies. Researchers showed that type 2 innate lymphocytes produce molecules that “switch on” white blood cells to make them produce an abundance of certain types of antibodies.
These antibodies coat cells as a defense against foreign invaders, giving the allergic person an immune system ready to attack at the slightest provocation. The number of every cell, molecule and antibody in this chain increases dramatically without butyrate.
make up for lost time
Butyrate must be given within a narrow window of time after birth—a few months for humans, a few weeks for mice—in order to prevent the proliferation of ILL2 cells and all that follows. If this window is missed and ILL2 cells proliferate, the remaining steps inevitably follow and remain with the person for life.
Now that researchers know these other steps, they have several potential targets for stopping this cascade, even after the supplementation period ends.
“We can now detect when a patient is about to develop lifelong allergies, simply by increasing their type 2 innate lymphocytes, and we can target those cell types instead of relying on butyrate supplements, which only work early in life,” said Ahmed Kabel, the study’s first author and a PhD candidate in the School of Biomedical Engineering, according to EurekAlert.
As Dr. McNagney and co-lead author Dr. Michael Hughes, a researcher in the School of Biomedical Engineering, point out, treating people’s allergies with antihistamines and inhalers relieves symptoms, but it doesn’t cure the disease. To make more lasting progress, researchers must target the cells and mechanisms that build this oversensitive immune system. Until now, there hasn’t been a selective way to do that.