The study, led by researchers from New York University School of Medicine, addresses the debate about how long H. pylori has been present in humans and, in particular, how long it has been in the New World. Some recent studies have suggested that Europeans first brought the bacterium to the shores of South America. But the new study provides strong evidence that migrating Asians introduced the bacteria to the New World where it has been transmitted generation after generation among the indigenous peoples.
"We know that the ancestors of present-day Amerindians migrated from East Asia to the New World more than 11,000 years ago," says Martin J. Blaser, M.D., Frederick King Professor and Chairman of the Department of Medicine, and Professor of Microbiology. "We used this historical event to help us understand how long the bacterium has been present in human populations. Our study shows that H. pylori has been present in humans for at least 11,000 years."
The study is published in this week's online edition of the Proceedings of the National Academy of Sciences and it will appear in print in the Nov. 12th issue of the journal.
Dr. Blaser and his NYU colleagues Guillermo Perez-Perez, DSc., Associate Professor of Medicine and Microbiology, and graduate students Chandrabali Ghose and David Pride, and researchers Maria Gloria Dominguez Bello, Ph.D., and Claudio M. Bravi, Ph.D., who are based in Venezuela and Argentina, respectively, examined genetic variations of H. pylori that are frequently present in East Asian populations, but not in Europeans. They did their analysis in two groups of Venezuelan patients: one group was representative of Amerindian (aboriginal) populations who lived in isolated communities in Amazonia and the other was a population of mixed European, African, and Amerindian origins who lived in Caracas.
The analysis is the culmination of two decades of research on H. pylori, a spiral-shaped bacterium that lives in the mucous layer lining the stomach where it can persist for decades. It is estimated that more than half the people in the world carry the bacterium in their stomach. Over the years, Dr. Blaser and longtime collaborator Dr. Perez-Perez have contributed greatly to understanding the biology of H. pylori. They analyzed how the bacterium damages the stomach, provided evidence showing that the bacterium is mainly transmitted in families, and elucidated genes in the bacterium that are associated with its virulence. One of those genes, vacA, was used in the present study. The gene is the subject of Ms. Ghose's work for her doctoral dissertation.
Their studies have shown that vacA and two other genes, babB and HPO638, contain variations associated with specific geographical populations and therefore can be used as a marker for these populations. Specific variations in the vacA gene, for instance, are found only in East Asian countries such as China, Korea, and Japan. Even when people from these countries migrate to North America, the strains of H. pylori that their children and grandchildren carry contain the variations of the gene specific for East Asia. People of European heritage do not carry strains with these variations.
Using their knowledge about the association of variations in the three genes in East Asian populations, the researchers analyzed DNA from the bacteria found in gastric samples obtained from patients during gastrointestinal endoscopy for dyspepsia, a condition characterized by nausea, pain, and burning in the stomach, among other symptoms. All patients signed a consent form to participate in the study.
There were 103 people from Caracas of European or mixed ancestry and 102 people from Venezuelan Amazonia who participated. The Amerindians in the study had come to a regional hospital in Puerto Ayacucho, a town on the Orinoco River in the Amazonian region.
In general, the researchers found that the overall pattern of genetic variations in all three genes revealed a Western European pattern in the group of patients from Caracas and, significantly, patterns associated with East Asia in the Amerindians. They also found Western genetic variations in the Amerindian group, suggesting that even in these isolated native populations there has been intermixing with Europeans.
Most importantly, the researchers found the genetic fingerprint of East Asia in the bacteria from Amerindians, which would be expected if migrating East Asians introduced the bacterium to the New World. Since it is known that these migrations occurred no more recently than 11,000 years ago, probably by traveling across the Bering Strait from East Asia, the researchers conclude that the bacterium must have existed in humans at least since that time.
Why has this bacterium existed for such a long time? The latest study contributes to the growing number of studies in the field of microbiology that attempt to answer questions about the long-term survival of bacteria and viruses. There is a general sense, says Dr. Blaser, that certain microbes that have long been present in humans may be less harmful than recently emerged microbes, such as HIV. The current study is consistent with the idea, he says, that H. pylori may have beneficial effects in humans and is one of the reasons it has survived.
The study was supported by grants from the National Institutes of Health, the Department of Veterans Affairs, The Institute for Urban and Global Health at NYU School of Medicine, and the Instituto Venezolano de Investigaciones Cientificas (IVIC) in Caracas, Venezuela.
Dr. Dominguez-Bello is affiliated with the Laboratory of Gastrointestinal Physiology, IVIC, Caracas. Dr. Bravi is affiliated with the National University of La Plata, La Plata, Argentina.
Journal
Proceedings of the National Academy of Sciences