The Hygiene Hypothesis and Autoimmune Diseases

Gut microbes indicate differences between children in developed and less-developed countries, new study of infants found.

There's an old saying that children will eat a pound of dirt by the time they grow up. While the idea may make the germaphobe shudder, it's becoming more clear that kids do need to be exposed to germs.

A new study compared the gut bacteria of children in different countries. The human gut--a major reason for the development of healthy immunity--is populated by many different kinds of bacteria. Researchers found children in more developed countries have different bacteria compared to those in less developed countries.

The hygiene hypothesis is the premise that the human immune system learns how to protect the body through regular exposure to bacteria, viruses and other pathogens. When the environment is too clean the immune system doesn't get enough “exercise.”

The result, some experts believe, is that allergies and autoimmune diseases have become more common.

In autoimmune diseases, the immune system attacks the body's own cells as if they were dangerous invaders. Typical autoimmune diseases include type 1 diabetes, asthma, rheumatoid arthritis and multiple sclerosis.

“If you look across the world geographically where incidence of autoimmune disease and allergies are high and then superimpose a map that shows where diarrheal diseases and bacterial infections occur, you’ll see very little overlap," co-first author Aleksandar Kostic, PhD, said in a press release. "That suggests that exposure to bacteria and other ‘bugs’ may play a pivotal role in the immune system, and that we might be able to understand what that role is by studying the human microbiome.”

Dr. Kostic is a postdoctoral fellow in the lab of Ramnik Xavier at the Broad Institute of MIT and Harvard.

Dr. Kostic and colleagues studied 222 infants in three different countries: Finland, Russian Karelia and Estonia. Finland is highly westernized, Karelia more traditional and agrarian, while Estonia has developed rapidly over the last 20 years since the Soviet Union dissolved.

The researchers collected stool samples and other lab tests from the infants. Parents completed questionnaires on breastfeeding, diet, allergies, infections and family history. The study was conducted over a period of three years.

Finland had six times as many cases of type 1 diabetes compared to Russian Karelia. In Estonia, as the economy has improved, autoimmune diseases have increased. These findings support the hygiene hypothesis.

Dr. Kostic and colleagues found that in Finnish and Estonian infants, a species of bacteria called Bacteriodes was most common in the infants' gut microbiomes. Children from Russian Karelia had high levels of a different species called Bifidobacteriaum. Russian Karelian infants also had a wider variety of bacteria in the gut microbiome compared to children from the other two countries.

Digging a little deeper, the researchers looked into the genetics of the different bacteria, specifically molecules called lipopolysaccharides (LPS). LPS molecules are embedded in the outer cell membrane of different types of bacteria. They are known to trigger the immune system.

E. coli, a bacteria commonly found in the human gut, is one of the strongest at triggering the immune system response. In Finnish and Estonian infants, the LPS from the Bacteriodes species was actually inhibiting E. coli from performing its natural immune system boost.

“In the Finnish and Estonian infants, where Bacteroides dominates, the gut microbiome is immunologically very silent,” Kostic said in the press release. “We believe that, later on, this makes them more prone to strong inflammatory stimuli.”

The study was published in the April issue of Cell.

Information on study funding and conflict of interest was not available.