Researchers probe Ötzi’s mummified gut tissue for clues about the gut bugs he carried.

Researchers probe Ötzi’s mummified gut tissue for clues about the gut bugs he carried.


The Iceman had a tummy bug

On the day that Ötzi the “Iceman” was murdered in the Tyrolean Alps of Italy about 5300 years ago, he had a full stomach—and a tummy bug. But it wasn’t just any gut microbe—this early farmer was infected with a particular ancient strain of Helicobacter pylori bacteria that is most similar to modern Asian strains. By sequencing the genome of this ancient pathogen, which can cause ulcers in people today, researchers have made a surprising discovery about Ötzi’s own history: His ancestors inherited bacteria from Asia rather than Africa, suggesting that the predecessors of early European farmers had intimate contact with Asians before they migrated to Europe.

H. pylori is probably the most successful bacterium to infect humans, and lurks in the guts of almost half of all people today. It causes ulcers, cancer, and gastritis—the inflammation of the lining of the stomach—in about 10% of people. In the rest, it can persist for decades, where there is some circumstantial evidence that it may be protective against asthma, allergies, and acid reflux. The microbe has inhabited humans’ guts for at least 100,000 years, based on the sheer diversity of stains that exist today. These strains cluster into seven different bacterial populations called prototypes around the world. Although H. pylori probably arose in Africa and was carried by modern humans as they settled around the world, it has been a mystery how different types of the microbe spread globally and how they are related to each other.

In Europe today, for example, the most common type (known as hpEurope) shares elements of DNA with types of H. pylori from both Africa and Asia. This had suggested that the European type was an ancient one, which evolved in the Middle East or other Asian crossroads more than 10,000 years ago. This may have happened when some hapless person was coinfected with both the African and Asian types—and the two strains hybridized into a new type before spreading into humans who then migrated to Europe, perhaps with the agricultural revolution 8000 years ago or so.

 There was no way to test this idea, though, without samples of ancient stomach tissue. Enter Ötzi, who was buried in ice for thousands of years—only to be discovered by hikers in 1991 when the ice melted. Imaging methods recently detected that his stomach was still preserved, giving researchers at the European Academy of Bozen/Bolzano (EURAC) in Italy their opportunity. In 12 biopsies of his remarkably well-preserved gut tissue (and stomach contents), they were able to isolate enough bacterial DNA to sequence the genome of H. pylori to relatively high resolution, as they report online today in Science.

When they compared Ötzi’s H. pylori genome with other types from around the world, they got a surprise—Ötzi’s type most closely resembled one from Asia, not those found today in Europe or Africa. This provides insights not only into Ötzi’s health, but also the movements of his ancestors. Ötzi’s own DNA most closely resembles that of early European farmers who originally came from the Middle East. But his bacterial strain most closely matches strains in India and South Asia today, which cluster together in the hpAsia2 population. Today’s hpEurope strain has far more DNA from the African type of H. pylori than does Ötzi’s Asian strain, notes lead author Frank Maixner, a microbial ecologist at EURAC.

He says this suggests a new scenario: The ancestors of early European farmers such as Ötzi must have carried H. pylori with DNA from Asian strains perhaps in the Middle East before they migrated to Europe. Then, new immigrants carrying African microbes arrived in Europe much later, after Ötzi lived. The two types of microbes mixed in these migrants, creating today’s European strain much more recently than expected.

This is significant, because it suggests that bacteria like H. pylori can evolve and adapt to new populations much more rapidly than expected, with gut-wrenching consequences in humans, says Christina Warinner of the University of Oklahoma, Norman, who was not involved with the work. "A surprising result of this and other recent ancient DNA studies is that many genetic traits and microbial strains that were once thought to be very ancient are actually quite recent."

The discovery also shows that it doesn’t take major migrations to bring in new microbes. This European strain may not have arrived on the continent with a major, known wave of new settlers from Africa; it could have been introduced by a few individuals who were coinfected with two strains, producing a particularly adaptive hybrid type that spread rapidly in Europe. “This shows there was an African lineage (of H. pylori) that had a very big transmission advantage—it spread right across Europe faster than we expected,” says Daniel Falush, a statistical geneticist at Swansea University in the United Kingdom, who was not involved with the work. Why it spread so rapidly is a mystery—perhaps it thrived on a dietary change, the spread of agriculture in which people settle in closer quarters than hunter-gatherers, or poorer hygiene helped it spread, he says.

The team also discovered that Ötzi, who was in his 40s, had harbored the H. pylori long enough to have a gut reaction to the microbe—his tissue showed the expression of 22 proteins that are associated with inflammation. He may have had gastritis or an ulcer. But he wasn’t too sick to stuff himself—his stomach was completely full of the meat of an alpine ibex when he died. “He ate quite a lot!” Maixner says.