Searching for microbes can become a weapon to detect cancer, studies show

Do a Google search for an image of a tumor and you will likely see a colorful cluster of cancer cells against a pale background of healthy tissue. But for Lian Narunsky Haziza, a cancer biologist at the Weizmann Institute of Science in Israel, the picture is very different. A tumor can also contain millions of microbes, representing dozens of species.

“I think this is an ecosystem,” she said. “It means that cancer cells are not alone.”

Scientists have long known that the human body harbors microbes, but they have always tended to treat tumors as if they were sterile. But in recent years researchers have abandoned that idea, demonstrating that tumors are full of microbes.

In 2020, several teams of researchers demonstrated that tumors harbor diverse mixtures of bacteria. And on Thursday, two studies published in the journal Cell found that tumors also contain many species of fungi.

This so-called tumor microbiome is turning out to be so characteristic and different in each type of cancer that some scientists hope to find early signs of occult tumors by measuring the microbial CNA they release into the blood. And some research indicates that microbes can make tumors more aggressive or more resistant to treatments. If this is proven, it may be possible to fight cancer by attacking a tumor’s microbiome in addition to the tumor itself.

“We need to reassess almost everything we know about cancer, looking at it through the lens of the tumor microbiome,” said Ravid Straussman, a biologist oncologist at the Weizmann Institute who collaborated with Narunzky Haziza on one of the new studies.

For the past two decades, scientists have mapped the microbes present in the human body, harvesting their DNA from mouth swabs, skin scrapings and feces. These surveys have identified thousands of species, totaling about 38 trillion cells, that live harmlessly in healthy people. It is now known that many organs that were previously seen as sterile have their own microbiomes.

While researchers investigated the healthy microbiome, cancer remained largely uncharted terrain. No one knew whether the millions of cells that make up tumors offered another habitat in which microbes could live.

In 2017, Straussman and his colleagues found bacteria living inside pancreatic tumors. They made the discovery when they tried to decipher how some tumors managed to resist a drug used in chemotherapy. They found that a species of bacteria that blocks the drug lived inside the tumors.

This discovery led Straussman and his colleagues to make a large study of the bacteria present in more than a thousand tumors of seven types of cancer. In 2020, they reported finding bacteria living in all seven types.

At the same time, a team of scientists from the University of California at San Diego conducted their own investigation, using a huge database of DNA collected from different types of cancer in the early 2000s.

Entitled Genomic Atlas of Cancer, the project aimed to help scientists find mutations in tumor genes that lead to the uncontrollable growth of cancer cells. But the San Diego team acknowledged that the raw data could also contain DNA from bacteria present in the tumors.

This, unfortunately, made it necessary to vascularize 6 trillion genetic fragments in the atlas in search of bacterial DNA fragments.

“It’s like trying to locate needles in a haystack when there are more straws than stars in the Milky Way,” commented team member Gregory Sepich-Poore.

The search took years, but it was worth it. Sepich-Poore and her colleagues found that a small percentage of the DNA fragments in 32 types of cancer belonged to bacteria, not humans.

After publishing their study in 2020, the researchers teamed up with Straussman’s team to find out whether the tumors also contained fungi.

Fungi are one of the great success stories in the history of evolution; there are an estimated 6.2 million species. They include the mushrooms that grow in forests, the yeasts used to ferment bread and beer, and the mold that gave us penicillin.

One of the characteristics shared by all fungi is the way they feed. Fungi release enzymes to break down organic material nearby and then absorb the material. Fungi can also produce immense numbers of spores, which are able to survive for years under inhospitable conditions of all kinds.

We are constantly exposed to fungi, whether by absorbing spores that end up on our skin or consuming foods that give fungus a ride. Most fungi will not take up residence in the human body.

“Many of them are just passing through,” explained immunologist Iliyan Iliev of Weill Cornell Medicine in New York.

But some species of fungi have adapted to live inside us. Skin fungi break down the oils we produce. Others feed on the sugars present in people’s mouths and digestive tracts. Scientists have already found other fungi also in the human body whose life is still a mystery. “We don’t know much, really,” Iliev said.

The San Diego and Weizmann Institute researchers looked for fungi in tumors in much the same way as they looked for bacteria, going back to studying the galaxy of DNA fragments in the Genomic Atlas of Cancer. Only this time they looked for fungal genes. They also examined Straussman’s collection of tumors.

All of the tumor types the scientists examined, from 35 different types of cancer, contained fungi, and each type had a unique combination of fungal species, the scientists reported in one of the studies released Thursday.

In the other new study, Iliev and his colleagues, working independently, found fungi in tumors in seven parts of the body: mouth, esophagus, stomach, colon, rectum, breasts and lungs.

New York University microbial ecologist Deepak Saxena, not involved with either study, was surprised by the abundance of the findings. “And I didn’t expect this amount of fungus in tumors,” he said. “This will change the way we look at cancer.”

Translation by Clara Allain