Study Contradicts Assumption That Ulcer Bug Has Always Plagued Humans

"My favorite interpretation of this finding is that the Spanish brought H. pylori to Peru when they conquered the Incan empire nearly 500 years ago and that the bacterium was not present in the ancestors who crossed the Bering Strait from Asia more than 10,000 years ago," says Douglas E. Berg, Ph.D., the Alumni Professor of Molecular Microbiology and professor of genetics at Washington University School of Medicine in St. Louis.

Berg and collaborators in Britain, China, Guatemala, India, Japan, Peru, South Africa, Spain, Sweden and the United States report their findings in the June issue of the Journal of Bacteriology.

H. pylori is carried by more than half the world’s population, and it can thrive in the stomach for years. Whereas some people suffer no apparent consequences, others develop peptic ulcer disease. Gastric cancer, the leading cause of cancer deaths in some developing countries, also has been associated with H. pylori.

Analyzing DNA from more than 500 strains from five continents, Berg’s group focused mainly on a region called the cag pathogenicity island. One part of this region contains apparently vestigial genes, and it varies in size because some strains have lost pieces of DNA whereas others have inserts. Also, some base pairs, the building blocks of DNA, have been substituted for others.

As well as measuring the size of the vestigial segment, the researchers examined the DNA sequences of cagA, a gene that lies just next to it, and vacA, which lies elsewhere in the chromosome. The cagA gene codes for a protein that, when phosphorylated, alters the internal communication system of human cells, whereas vacA codes for a toxic protein.

The DNA analysis classified the H. pylori isolates into five types. Type I DNA motifs predominated in the strains from Spain, Peru, Guatemala and native Africans. Type II motifs were most common in the Chinese and Japanese strains, whereas type III motifs predominated in the Indian strains. Each of the three motifs was common in the strains from northern Europe. The rare type IV motif showed up in one English strain and two strains from West Virginia, and the type V motif was found in a few of the Indian strains. "So we can type H. pylori strains from different societies by differences in their DNA," Berg says. "One of the most striking differences was between strains from eastern Asia – China and Japan – and strains from Amerindians in Peru."

Berg speculates that H. pylori might have infected humans when agriculture brought animals and people into closer contact. "Many other diseases – tuberculosis, whooping cough, measles, mumps and chicken pox – are of animal origin and probably came into the human population when our ancestors started to practice agriculture and when their population densities increased," he says.

Until now, scientists have assumed that humans acquired H. pylori during their evolution from pre-human ancestors. "People haven’t paid any attention to the possibility that human H. pylori infection might have become widespread only in more recent history," Berg says.

His results are compatible with the idea that genetic differences between strains in different parts of the world reflect selection for different types of CagA protein in different animals hosts – either domesticated animals or rodent pests that came to live with early agriculturists. "For example, the ancestors of European strains of H. pylori might have come from mice or sheep, whereas the ancestors of various Asian strains might have come from cats, pigs or Mongolian gerbils," he says. "All of these animals can be infected with at least certain H. pylori strains recovered from human patients."

In another paper in the same issue of the Journal of Bacteriology, Berg and collaborators describe genetic differences between strains isolated from patients in Calcutta, India, and those from Europe and elsewhere in Asia. Their analysis of vacA was particularly instructive, revealing motifs that were present only in the Indian strains. "So the Indian motif is distinctive," Berg says, "reflecting either historic separations of people in India from people in Spain and in eastern Asia or selection for different traits in different ancestral animal hosts."