Excess Hygiene May Weaken Developing Immune Systems
New research suggests that childhood exposure to germs may help strengthen the immune system and protect children from developing allergies and asthma in later life.
The latest research on mice supports the “hygiene hypothesis,” which states that the lack of early exposure to bacteria increases vulnerability to auto-immune diseases, and contends that such diseases are more prevalent in the developed world where the frequent use of antibiotics reduces children’s exposure to microbes.
Scientists compared the immune systems of one group had been exposed to a normal bacteria environment to another group of “germ-free mice,” and found that the mice living in normal environments had a significantly healthier immune systems than mice living in ultra clean environments.
Researchers found that the germ-free mice had exaggerated inflammation of the lungs and colon, resembling asthma and ulcerative colitis in people, which was caused by the hyperactivity of an invariant natural killer T cell.
The findings also show that a lack of exposure to microbes in early life cannot be compensated for in adult mice.
However, scientists from the latest research found the fragile immune systems of germ-free mice could still be restored to normal if they were introduced to microbes in the first few weeks after they are born.
"These studies show the critical importance of proper immune conditioning by microbes during the earliest periods of life," one of the study's senior authors, Dr. Richard Blumberg of Brigham and Women's Hospital said in a statement released on Thursday. "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."
Researchers focused on the CXCL16 signaling protein that has been linked to inflammation and natural killer T cells, and found that CXCL16 expression was more active in the colon and lung tissue of the germ-free mice when compared to normal mice, and that blocking its expression reduced the numbers of the killer T cells and the amount of tissue inflammation.
“There probably are some specific organisms and molecules produced by those organisms that influence this pathway,” co-research Dennis Kasper, a microbiologist at Harvard Medical School in Boston, Massachusetts told Nature. “It seems like there’s something that sets the thermostat at a very, very young age, but we don’t know what it is.”
Researchers said that the findings suggest that a lack of early exposure to certain microbes alters the DNA strand to increase CXCL16 expression which will increase the numbers of killer T cells leading to more inflammation.
"It's really a huge leap to go from mice to humans, but they are both mammals and there are definitely parallels in their immune systems," Kasper told LiveScience.
While other scientists are skeptical of whether a similar pathway of CXCL16 over expression is shown in people, the results “complement what we see in epidemiology,” Erika Von Mutius, head of the Asthma and Allergy Department at Munich University Children’s Hospital in Germany told Nature. It supports the idea that the micro biome is very important and the age of exposure is decisive.”
Investigators said that their findings confirm the “hygiene hypothesis” that the protection provided by early-life exposure to microbes was long-lasting, and as the world became progressively hygienic there was also an increase in people diagnosed with autoimmune diseases such as hay fever, asthma and inflammatory bowel disease.
According to the U.S. Centers for Disease Control and Prevention the number of children diagnosed with asthma doubled from 3.6 percent in 1980 to 7.5 percent in 1995, and by 2005 12.7 percent of children had been diagnosed with asthma.
Daniel Peterson an immunologist at Johns Hopkins Medical Institute in Baltimore, Maryland told Nature that the study has limitations because it is impossible for any person to be as “germ-free” as the mice used in the study. However, he finds the study to be provocative.
“The striking finding is that you have this long-term persistent elevation of iNKT cells that isn’t reversed later with conventional microbes,” Peterson said. “It really opens up a lot of questions about how long this window lasts and which microbes are involved.”
The results were published on Friday in the journal Science.