Nav: Home

Stunning diversity of gut bacteria uncovered by new approach to gene sequencing

December 14, 2015

A collaboration between computer scientists and geneticists at Stanford University has produced a novel technique for mapping the diversity of bacteria living in the human gut.

The new approach revealed a far more diverse community than the researchers had anticipated. "The bacteria are genetically much more heterogeneous than we thought," said Michael Snyder, PhD, professor and chair of genetics.

Any two humans typically differ by about 1 in 1,000 DNA bases, whereas bacteria of the same species may differ by as many as 250 in 1,000, Snyder said. "I don't think people realized just how much diversity there was. The complexity we found was astounding," he said.

In the past, researchers could only study bacteria that would grow in the lab. But the vast majority of bacterial species will not grow on traditional culture medium. As a result, the true diversity of bacteria -- not only in the human gut but throughout the living world -- has remained largely unexplored.

In recent years, a genomics approach has begun to reveal diverse communities of new bacterial species growing nearly everywhere biologists have looked. Modern gene sequencing has tantalized biologists with hints of bacterial worlds as biodiverse as any tropical rain forest. Yet the limitations of current technologies have created only a blurry picture and prevented researchers from seeing all that is there.

Of particular interest are the bacteria that live in our intestines. Some communities of bacterial species in the gut have been associated with good health, others with any of a long list of conditions -- including obesity, Type 2 diabetes, bowel disease and liver disease. And some are outright pathogens that can sicken and even kill, such as certain strains of E. coli or the bacterium that causes cholera. Given their importance to human health, the ecological communities of bacteria that live inside us and on our skin have come under increasing scrutiny.

A Stanford team has overcome some of the limitations of current sequencing technology to create a sharper picture of the bacterial community, or microbiome, of the human gut. The team used new computational approaches and "long-read" DNA sequencing to reveal the diversity of bacteria in the gut microbiome of a single male human.

A paper describing their work will be published online Dec. 14 in Nature Biotechnology. The lead author is Volodymyr Kuleshov, a doctoral student in computer science at Stanford. Snyder, the Stanford W. Ascherman, MD, FACS, Professor in Genetics, is co-senior author with professor of computer science Serafim Batzoglou, PhD.

Problem posed by short snippets of DNA

Current DNA sequencing technology looks at very short snippets of DNA sequences. If you are looking at just one genome -- from a bacterium or a single person, for example -- you can assemble the snippets into a whole genome, much as you might painstakingly assemble a jigsaw puzzle.

But when you are looking at snippets from a mass of different bacteria from the human gut, assembling those snippets is like trying to assemble 100 jigsaw puzzles from a pile of pieces from all 100 puzzles jumbled together, explained Snyder. Any two pieces could be from completely unrelated puzzles -- analogous to different species of bacteria -- while others could be from multiple copies of the same puzzle -- analogous to the same species of bacteria.

If that sounds difficult, the real challenge is being able to tell apart the pieces from puzzles that are almost the same but not quite. And that's what the researchers' new technique does. "We assembled one whole genome from this big gemisch, which has never been done before," said Snyder.

"We normally sequence 100 DNA bases off a 300-base fragment," he said. "You just get snippets of information." But using a new informatics approach, Snyder and Batzoglou's team stitched together larger segments of the genome. "We have a sophisticated algorithm that lets us put together all these pieces -- first assembling the snippets into longer, 10,000-base pieces, then the 10,000-base pieces into still-longer fragments, and then those into whole genomes," Snyder said.

Such long sequences of DNA can span hundreds or even thousands of genes that couldn't be recovered from short-read sequencing; they can help classify bacteria and other organisms by how related they are to one another; and the long sequences also help identify rare bacteria that might be missed by current methods. "We could assemble either entire genomes or at least very, very large chunks of the genome," said Snyder.

Great bacterial diversity

Being able to see such long sections of the genome means being able to distinguish not only different species of bacteria, but different strains of the same species. The team tested the technique on a standardized sample of known bacteria and then took it for a spin on the gut contents of a human male. The result revealed not only lots of species, but many different strains of the same species. One bacterial species, for example, included five separate strains -- all from one person.

The consequences of having so many different strains are hard to predict, but some strains may be more or less likely to make people ill. For example, many strains of E. coli bacteria live harmlessly and even helpfully in the human gut, while others are lethal. Being able to tell one strain from another could help researchers determine which strains are dangerous and why.

Right now, researchers who want to study virulence have to isolate that strain and then grow it in the lab. But some bacteria don't grow easily in the lab. If researchers can study the genes that contribute to virulence directly in the mixture of bacteria from a human gut sample, they don't need to isolate it and grow it in a pure culture. "When you assemble the whole genome, you have a better idea of what the pathogenic genes are. I think it's going to be very, very powerful for understanding the genetic basis of pathogenesis," said Snyder.

The new approach will make it easier to construct the evolutionary history of strains of infectious bacteria or viruses, such as Ebola. And the approach can be used in the field to study microbial diversity in healthy people and other animals, as well as in plants, water and soil. "When we put this together now, using these long reads, it's like an IMAX movie," Snyder said. "You can see the whole thing much more clearly than with what we do now, which is like an old black-and-white TV."
Other Stanford-affiliated authors of the paper are postdoctoral scholars Chao Jiang, PhD, and Wenyu Zhou, PhD, and research associate Fereshteh Jahaniani, PhD.

This work was supported by National Institutes of Health (grant 3U54DK102556). Stanford's Department of Genetics in the School of Medicine and the Department of Computer Science in the School of Engineering also supported the work.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit The medical school is part of Stanford Medicine, which includes Stanford Health Care and Lucile Packard Children's Hospital Stanford. For information about all three, please visit

Stanford University Medical Center

Related Bacteria Articles:

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.
Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.
Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.
Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.
Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.
How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.
The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?
Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.
Bacteria uses viral weapon against other bacteria
Bacterial cells use both a virus -- traditionally thought to be an enemy -- and a prehistoric viral protein to kill other bacteria that competes with it for food according to an international team of researchers who believe this has potential implications for future infectious disease treatment.
Drug diversity in bacteria
Bacteria produce a cocktail of various bioactive natural products in order to survive in hostile environments with competing (micro)organisms.
More Bacteria News and Bacteria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 3: Shared Immunity
More than a million people have caught Covid-19, and tens of thousands have died. But thousands more have survived and recovered. A week or so ago (aka, what feels like ten years in corona time) producer Molly Webster learned that many of those survivors possess a kind of superpower: antibodies trained to fight the virus. Not only that, they might be able to pass this power on to the people who are sick with corona, and still in the fight. Today we have the story of an experimental treatment that's popping up all over the country: convalescent plasma transfusion, a century-old procedure that some say may become one of our best weapons against this devastating, new disease.   If you have recovered from Covid-19 and want to donate plasma, national and local donation registries are gearing up to collect blood.  To sign up with the American Red Cross, a national organization that works in local communities, head here.  To find out more about the The National COVID-19 Convalescent Plasma Project, which we spoke about in our episode, including information on clinical trials or plasma donation projects in your community, go here.  And if you are in the greater New York City area, and want to donate convalescent plasma, head over to the New York Blood Center to sign up. Or, register with specific NYC hospitals here.   If you are sick with Covid-19, and are interested in participating in a clinical trial, or are looking for a plasma donor match, check in with your local hospital, university, or blood center for more; you can also find more information on trials at The National COVID-19 Convalescent Plasma Project. And lastly, Tatiana Prowell's tweet that tipped us off is here. This episode was reported by Molly Webster and produced by Pat Walters. Special thanks to Drs. Evan Bloch and Tim Byun, as well as the Albert Einstein College of Medicine.  Support Radiolab today at