Exploring the human gut microbiome

Scientific interest in this diverse world of bacteria has flipped from fear to fascination
Lab intern Andrew Tagle
Andrew Tagle is an intern in the Lampe Lab, which, by studying the microbiome of the human gut tract, seeks to understand the mechanisms by which components of the diet, particularly plant foods, alter cancer risk factors. Photo by Robert Hood / Fred Hutch News Service

When Dr. Robert Day was a medical student at the University of Chicago, the microbial contents of the human gut was something for a young surgeon to fear. In the era when antibiotics were few, a nick of the gut risked peritonitis, a potentially deadly infection for the patient.

Fast forward to today at Fred Hutchinson Cancer Research Center, the institution that Day led as president and director from 1981 to 1997, and scientific interest in the human gut ―and its teeming microbial residents ― has flipped from fear to fascination.

To honor his 85th birthday, Day had his pick of topics for a scientific symposium to be held at Fred Hutch. His choice: the human gut microbiome.

The microbiome is a diverse world of trillions of bacteria whose complex interactions keep us all alive, occasionally threaten our health and may hold secrets to preventing cancer or improving the lives of patients going through treatment for it.  Somewhere down there, perhaps, are the launching pads for cures.

“This is a very interesting subject,” said Day, who remains a full member of the Hutch faculty. “Every week there is something new.”

Scientists have been curious about the invisible critters inside us since Antonie van Leeuwenhoek, a Dutch maker of microscopes, peered through his primitive lenses in the 1680s. He spotted living creatures, “animalcules,” in samples of his own poop. Using state-of-the art tools of microbiology, scientists have discovered only recently that we harbor a stunning variety of gut bugs. Our insides are an ecosystem of vast complexity, and our bug populations can be very different from one human being to the next.

Despite the development of remarkable laboratory tools that can identify millions of different gut bug species by their genetic markers, the peculiar source material for microbiome research remains much the same, and hence, research in this field is not for the faint of heart, nor queasy of stomach.

'Spit, vomit and poop'

“Spit, vomit and poop,” was the nickname of a famous Stanford study that set out to determine which route the seemingly villainous bacteria Helicobacter pylori used to jump  from person to person.  The culprit was the vomit, said Fred Hutch researcher Dr. Nina Salama, a speaker at the symposium. Her talk underscored just how dynamic and puzzling is this ecosystem now under exploration.

Notorious as the first bacteria to be labeled a carcinogen, H. pylori is a leading cause of stomach cancer. But Salama’s work is showing that the cancer-causing mechanics of this bug are tied up in complex interactions with other bugs, enzymes and tissues of their human host. Most people infected with H. pylori do not get cancer.

“We have to be less ‘one-bug-centric,’” she said. While H. pylori clearly raises stomach cancer risk, studies have found that this same bug may actually protect the adjacent esophagus from adenocarcinoma, an esophageal cancer that has been rapidly increasing as H. pylori infections and related stomach cancers have been on the decline. Salama and other researchers are sifting biochemical clues to figure out why.

Of the millions of bacteria, fungi, protozoa, and other microbes that may populate our digestive tract, only about 1,400 are known pathogens. Many of these friendly microorganisms help us break down the foods we eat, release vitamins, and outcompete the bad guys. Each of us may have a microbial community inside us with more than 1,000 varieties of bugs, collectively weighing in at about 3 pounds – the same weight as an adult brain. 

Dr. Johanna Lampe
Dr. Johanna Lampe Fred Hutch file

“There is an eye-opening aspect to this research that cuts across many disciplines,” said Dr. Johanna Lampe, associate director of the Public Health Sciences Division at Fred Hutch and symposium moderator. “One can only begin to fathom what the impact may be.”

Her own work, which focuses on the role of diet in cancer prevention, is exploring how communities of bacteria my influence metabolism, sometimes releasing beneficial nutrients, other times chemicals that might cause harm.

There’s a reason for the sudden interest in the human microbiome, a term said to be coined just 15 years ago by the late Nobel laureate Dr. Joshua Lederberg. Only recently, the gene-sequencing tools that brought us the map of the human genome opened up the world of the microbiome. Previously, most bacteria inside our gut were not identified since they couldn’t be cultured for study in a lab dish. Now, they don’t have to be grown. Their genetic signatures can be plucked and sequenced just like the roughly 22,000 genes that are found in every cell of the human body.

Dr. David Fredricks of the Fred Hutch Vaccine and Infectious Disease Division showed symposium attendees just how important this new avenue of research is becoming. Fredricks is studying patterns of gut bugs in cancer patients who have blood stem cell transplants. Many of them have had rounds of antibiotics prior to their transplant and may be treated with them afterward. His research shows that the makeup of gut bug populations can vary significantly among patients after antibiotic treatment, and that analysis of these patterns might be used to predict the risk of graft-vs.-host disease, a potentially deadly complication where donor cells attack the host.

Stool samples in the lab
Stool samples are analyzed in the Lampe Lab. Photo by Robert Hood / Fred Hutch News Service

Keynoting the Fred Hutch symposium was Dr. Lita Proctor, program director for the Human Microbiome Project at the National Institutes of Health, who made it clear this fascinating field is just beginning to blossom. The goal of the federally funded program is to “create a toolbox” of resources to help scientists. Initially, the Human Microbiome project was focused on identifying the communities of microbes in humans. Now, she said, the emphasis of research is “what are they doing?”

'They don't live alone. They act as communities.'

One of the discoveries emerging from work on the human microbiome is just how important it is to understand the interactions of microbes. “They don’t live alone. They act as communities,” she said.

She noted that “we’ve all co-evolved with microbes,” creatures that first appeared on Earth 3.5 billion years ago. Our growing understanding of the importance of these bugs now extends to outer space.

As different teams of astronauts pass through the International Space Station, each one carries its own microbiome, and like all humans, sheds skin cells teeming with bacteria, which raises health concerns.

“The space station was never built to be sanitized between deployments,” she said. “Apparently they did a swab, and every little corner and nook and cranny is just loaded with stuff,” she said. “So the concern is that the International Space Station is becoming now like a day care center … NASA is quite concerned about the astronauts and their biomes.”

Sabin Russell is a staff writer at Fred Hutchinson Cancer Research Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT, and a freelance writer for the New York Times and Health Affairs. Reach him at srussell@fredhutch.org.

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