The New Hygiene Hypothesis

Bengt Björkstén has a gold mine of feces in his freezer. Over the past 11 years, the Swedish pediatrician and immunologist has been carefully collecting fecal samples from a cohort of children living in Sweden and neighboring Estonia. The samples harbor a wealth of information on the children’s microbial inhabitants, which have been shown to play a vital role in immune function. Björkstén hopes that new technologies that allow scientists to analyze microbes more precisely than ever before will reveal why allergy rates in Sweden and other wealthy nations, including the United States, have risen dramatically over the past 50 years, while rates in historically poorer nations, such as Estonia, have not.

His findings could provide a new twist on the hygiene hypothesis, which suggests that rising allergy rates are linked to our more antiseptic, modern lifestyle. If scientists can find the elusive x factor that either protects against allergies or increases risk for them, they may be able to recreate it, perhaps by dosing mothers or babies with healthy bacteria, known as probiotics. “We’re on the verge of a revolution in understanding the human microbiome,” says Björkstén. “The key to understanding these diseases may be in the gut, rather than in the environment.”

A host of explanations have been put forth to account for rising rates of allergy and asthma, including reduced rates of breast feeding, parents who smoke, and worsening pollution. But as most of these factors have been ruled out–poorer cities with high levels of pollution often have lower allergy levels, for example–an alternative explanation has taken the lead. Scientists suggest that now that many of the most harmful bugs in our environment have been eradicated with modern sanitation and medicine, our immune systems turn their attack on usually harmless molecules, such as those in cat dander or dust mites.

Support for the hygiene hypothesis comes from studies showing that pre- and postnatal exposure to pets, farms, and older siblings protects against allergies. But as scientists are beginning to better understand the beneficial bacteria that live within us–and the role that it plays in immune development–a new twist on the hygiene hypothesis is emerging. It may be that these environmental factors impact the microbes that colonize newborn babies, which in turn affect immune development and risk for allergy. “The first microbes we put in our GI tract can settle there,” says Josef Neu, a physician and scientist at the University of Florida, in Gainesville. “Are there long-term effects to microbiome manipulation? We need to use new techniques to look at this much more broadly.”

It’s here that Björkstén’s frozen treasure trove will come in handy. For more than a decade, the pediatrician has been collecting fecal samples–bacteria in stool are a measure of the microbial inhabitants of our gut–as well as extensive medical records and allergen-test results. Because living conditions in Estonia are similar to those in Sweden 40 years ago, the Estonian children provide a snapshot of the past. Comparing the two populations is starting to reveal how our gut ecology is changing over time and how those changes impact disease. “These are incredibly precious moments to understand microbial evolution in humans,” says Jeff Gordon, a scientist and gastroenterologist at Washington University in St. Louis.

Initial studies of the children’s gut microbes using traditional microbiology approaches have yielded tantalizing clues into their role in allergy: the number and diversity of microbes inhabiting a baby’s gut soon after birth seem to predict his likelihood of later developing allergic disease. In addition, babies born in urban environments have fewer microbes and fewer diverse microbial communities than those born and raised on farms. The same is true for babies born in Sweden versus those born in Estonia.

Björkstén, who named the pattern the “immunologically mediated syndrome of affluence,” now aims to analyze the samples using metagenomics, which assesses microbial populations without having to grow them in the lab–a major impediment to the research until very recently. (See “The Next Human Genome Project: Our Microbes.”) This approach will generate a much more extensive microbial profile and allow scientists to look for specific patterns linked to allergy. If they can pinpoint the precise factors that lead the immune system awry and boost risk for immune disorders, the researchers may be able to prevent them. “No one wants to go back to a poor state of hygiene with maternal sepsis in the maternity ward,” says Björkstén. “So we need to solve this another way.”