Selective losses of human-associated microorganisms may be responsible for a wide range of modern ailments, including esophageal diseases, obesity, asthma, and the epidemic spread of high-grade pathogens, according to Martin Blaser from New York University Langone Medical Center in New York City.
He cites Helicobacter pylori as a prime example of this phenomenon. "H. pylori, which should be the numerically dominant residents of the stomach environment, have been disappearing with remarkable speed in developed countries," he says. This loss is bringing "significant gastric secretory, hormonal, and immune changes," including some that harm human health.
In two to three generations, humans moved from near-ubiquitous colonization by H. pylori-more than 80% of people carried them-to rates in the single digits for children born in the United States and Western Europe, Blaser says. "This is an unprecedented change in human microecology," and reflects more sweeping alterations across the human microbiota, according to Blaser and Stanley Falkow from the Stanford University School of Medicine in Stanford, Calif. They attribute this to multiple factors, including cleaner water, smaller families, births involving a higher percentage of Caesarean sections, a reduced frequency in breastfeeding, and the widespread use of antibiotics, especially among pregnant women and children. Details appear in the December 2009 Nature Reviews Microbiology (doi: 10.1038/nrmicro2245).
"Over the long history of its relationship with humans, H. pylori-provoked inflammation has progressively decreased the numbers of gastric acidsecreting glands, with a consequent decline in acid production," Blaser says. This decline is not all bad; it has led to a drop in incidence of illnesses with long latent periods such as gastric cancer. However, the tradeoff is a rise in gastroesophageal reflux disease (GERD) and its consequent risks of Barrett's esophagus and gastric adenocarcinoma. The stomach produces the hormones ghrelin and leptin, both of which have multiple roles in energy homeostasis, Blaser says. "Children growing up in developed countries have little gastric H. pylori-mediated regulation of these adipokines, which may contribute to our current epidemic of childhood obesity, type 2 diabetes, and related metabolic syndromes." Furthermore, he adds, "We're exposing young children to microbiome-altering antibiotics. Because this practice increases feed efficiency in poultry, cattle, and pigs, it might also impact on our escalating numbers of overweight children." "People colonized with H. pylori have enhanced T-cell populations, particularly the subsets that regulate immune functions," Blaser continues. For example, H. pylori-positive individuals- especially those carrying cag-positive strains-have lower risks of childhood asthma, allergic rhinitis, and skin allergies than do their H. pylori-deficient peers, he says, citing epidemiological studies.
As H. pylori or other microbiota disappear from an anatomic site, other microbial tenants take over. Pneumococcal vaccine use provides a good example of niche shifting, according to Falkow. "A growing body of evidence suggests that the encapsulated pneumococci and Staphylococcus aureus are ecological competitors; thus widespread immunization against Streptococcus pneumoniae has probably helped facilitate the spread of aggressive communityacquired, methicillin-resistant S. aureus that we're seeing today."
H. pylori, S. pneumoniae, and S. aureus attract constant scrutiny; however, countless other microbial shifts are taking place under the radar. Blaser and Falkow hold that the major factor for modern allergic and metabolic disease is not our decreased exposure to immune-stimulating microbes in food, air, water, or soil as postulated by the "hygiene hypothesis." Rather, they attribute the recent trends to the loss of our ancestral microbiota.
The Human Microbiome Project (see http://www.human-microbiome.org/) will help to ascertain how the microbiota is changing, say Blaser and Falkow, stressing that "it's crucial to improve our understanding of the relationships between humans and our microbiota so that we can better assess the risks and benefits of modifying its composition, either deliberately or inadvertently."
Marcia Stone is a science writer based in New York City. More of her work can be seen at http://www.mstoneworks.net.