Coevolution between humans, bacteria reduces gastric cancer risk, research suggests

Working with colleagues in Columbia and the U.S., Scott Williams, PhD, a professor of genetics at the Geisel School of Medicine and the Institute of Quantitative Biomedical Sciences (iQBS) at Dartmouth, and his graduate student Nuri Kodaman discovered that the risk of developing gastric cancer depends heavily on both the ancestry of the person and the ancestry of Helicobacter pylori with which that person is infected. About half of the world's population is infected with H. pylori. The microbe usually only causes minor gastric inflammation, but it is also the primary cause of gastric cancer, which is the second-leading cause of death by cancer worldwide.

Williams' research team studied 233 people from two populations in Colombia, one located in the mountain village of Tuquerres and the other in the coastal village of Tumaco. Rates of H. pylori infection in the two communities are similar (about 90%), but the rate of gastric cancer is about 25 times higher in the mountain community. The researchers classified the ancestry of the people in both villages and of the H. pylori in each area. In the coastal village, the human population was primarily of African descent. The dominant component of the H. pylori also came from Africa. In the mountain village, the people were largely Amerindian and had very little African ancestry, and the H. pylori was predominantly derived from Europe.

The researchers examined the connections between human ancestry, the strains of H. pylori, and the severity of gastric disease and made several important findings: First, among both populations, people of European or Amerindian descent were at greater risk of developing more severe lesions than were people of African descent. Second, in the mountain community, where most people were of Amerindian or European descent, those infected with African-derived H. pylori had worse outcomes than those infected with predominantly European strains. And third, people from either village who had the lowest percentage of African ancestry had lesions that were more severe if they had H. pylori with a high proportion of African ancestry.

"The interaction between H. pylori and human ancestry entirely accounted for the difference in geographical disease risk," said Kodaman, a graduate student based at Vanderbilt University, who is working and studying under Williams in the Department of Genetics at Geisel.

Based on their findings, the researchers concluded that coevolution among humans and H. pylori reduced gastric cancer disease risk in the people of African descent. People of Amerindian descent would have been exposed to European or African strains of H. pylori much more recently, meaning that there would not have been time for coevolution to take place and explaining the worse outcomes among the villagers in the mountain community.

"The historical geographic movement of populations continues to influence health and cancer risk in modern Americans," the authors noted in the paper, which was published in January in Proceedings of the National Academy of Sciences.

"These data provide a remarkable example of coevolution between humans and the natural world; in particular, the microbial environment," said Jay Dunlap, PhD, chair of the Department of Genetics and a professor of genetics and of biochemistry.

Williams, who studies diseases that are differentially distributed among human populations, uses the tools of evolutionary biology to examine the role that genetics plays in health disparities. He has often conducted research on genetic variation within Africa, especially as it relates to diseases that affect people of African descent more frequently than other populations. His work, he said, "has helped to illuminate human evolutionary history and serves to bring disease presentation into an evolutionary perspective." The research in Colombia, for example, may help explain why the rate of gastric cancer is relatively low in Africa despite the high rate of infection with H. pylori, a phenomenon referred to as the "African enigma."

"Dr. Williams' study is particularly important in a world where geographic barriers continue to be broken down," said Robert A. Kramer, PhD, an assistant professor of microbiology and immunology at Geisel. "These fascinating, clinically relevant results argue for more in-depth and broad-spectrum analyses of the coevolutionary relationships between hosts and the microbes that colonize and infect them. One wonders how many human diseases are caused by perturbations in host-microbe interactions, and how we could use this knowledge to prevent and/or treat such perturbations. It is exciting to think about the specific mechanisms that could drive these phenotypes."

Jason H. Moore, PhD, Third Century Professor, a professor of genetics and of community and family medicine at Geisel, director of iQBS, and associate director of Norris Cotton Cancer Center, said that "bacterial cells outnumber human cells many-fold. This study is just the beginning of understanding how our microbiome changes our risk of disease."

The scientific knowledge gleaned by the researchers may eventually help clinicians to better prevent gastric cancer among diverse world populations by using the ancestry of both an individual and the strain of H. pylori as risk factors for the development of the disease. "Coevolutionary relationships are important determinants of gastric disease, and the disruption of these relationships may lead to subsequent adverse health outcomes," the authors noted.