The “hygiene hypothesis” suggests exposure to diverse types of microbes may protect against developing diseases caused by allergens, but a new study in mice reveals that adults’ exposure to diverse microbes and allergens may in fact worsen certain allergic conditions.

“Our data suggests that it’s important to think about how we go through the world and protect ourselves from exposure to microbes, because depending on your condition, if you’re moving from a clean to a dirty environment, or dirty to clean environment, you might have a different response in terms of developing allergic disease,” said Avery August, Ph.D. ’94, professor of immunology in the College of Veterinary Medicine and deputy provost. August is senior author of the study published Feb. 23 in the Journal of Immunology. 

The “hygiene hypothesis” posits that exposure to a diverse array of microbes protects against allergic-type diseases, according to the paper. For example, the hypothesis would suggest that growing up on a farm or in less-clean environments protects against allergic responses. Published epidemiological and experimental data has provided strong support for this hypothesis. However, the current study finds that such protection may be nuanced and could depend on life stage and timing of exposure. 

“The critical question is, where’s that break point between when exposure to broad diversity of antigens is protective and when it may aggravate?” August said. 

In the study, the researchers subjected mice to airway exposure of house dust mites to see if they would develop allergic airway inflammation, a model used in mice to study human asthma. 

They used so-called “specific pathogen free” mice, which are mice raised in clean environments, with lower exposure a broad diversity of microbes and free from certain disease-causing pathogens. In this way, researchers can ensure infections don’t interfere with experiments. 

These clean mice were then co-housed in the same environment with store-bought mice that are exposed to a wide range of microbes, which they then share, due to proximity, with the pathogen-free mice. The specific pathogen-free adult and newborn mice were then also exposed to house dust mite allergens, to see if they developed allergic airway inflammation.

They found that exposure to microbes as adults worsened the development of allergic airway inflammation compared to newborns exposed to these microbes. In next steps, the researchers hope to test the timing as mice age to see when protection from microbial exposure might wane, whether specific classes of microbes play a role in disease development and how the effects discovered in the study might apply to other types of disease. 

Jessica Elmore, Ph.D. ’21, a former member of August’s lab, is the paper’s first author. 

The study was funded the National Institutes of Health, the Howard Hughes Medical Institute and the Alfred P. Sloan Foundation.