Researchers have long suspected that the global spike in allergic and autoimmune diseases is linked to a decline in exposure to germs in childhood, especially in urban settings. But until now, no one has been able to directly demonstrate a biologic support or a mechanistic basis for the theory, known as the hygiene hypothesis. 

In a paper published online March 22 in the journal Science, researchers at Brigham and Women’s Hospital and Harvard Medical School provide new evidence supporting the hygiene hypothesis, as well as a potential mechanism.  

The researchers compared the immune systems of mice lacking bacteria or any other microbes with those of mice living in a normal environment with microbes. They found that germ-free mice had exaggerated inflammation of the lungs and colon resembling asthma and colitis, respectively. The cause was hyperactivity of a unique class of T cells previously linked to these disorders in both mice and humans. 

Importantly, the researchers found that exposing the germ-free mice to microbes during their first weeks of life, but not when exposed later in adult life, led to a normalized immune system and prevention of diseases. Moreover, the protection provided by early-life exposure to microbes was long-lasting, as predicted by the hygiene hypothesis. 

“These studies show the critical importance of proper immune conditioning by microbes during the earliest periods of life,” said Richard Blumberg, HMS professor of medicine and chief for the BWH Division of Gastroenterology, Hepatology and Endoscopy. “Also, now knowing a potential mechanism will allow scientists to potentially identify the microbial factors important in determining protection from allergic and autoimmune diseases later in life.”  Blumberg and Dennis Kasper of the Channing Laboratory at Brigham and Women’s were senior authors on the paper.

— R. Alan Leo