Researchers can now do gargantuan gut check

By Emilia Costales

Rob Knight, a professor in the University of Colorado Boulder’s department of chemistry and biochemistry, and a faculty member at the BioFrontiers Institute, is sharing the largest-known dataset on the human microbiome and the software key to understand what it may reveal about the role of the millions of bacteria living in and on the human body.

The data are from the American Gut Project and includes information from more than 3,000 participants, 101 million DNA sequences and 27 gigabytes of sequencing information.

The data have been de-identified to remove personal information, which was collected from 3,238 participants ranging in age from newborns to octogenarians, and from Paleo dieters to omnivores. The American Gut Project summary, dataset and processing notebook can be found at http://americangut.org.

Scientists are becoming increasingly acquainted with the 100 trillion or so microbes that live on and in our bodies. These bacterial cells outnumber our human cells by as many as 10 to 1.

There are more than 1,000 known bacterial species in the human microbiome, which also include viruses and fungi. The diversity of a microbiome is important. The more species of bacteria thriving in and on a person, the better.

The microbiome has been linked to a broad spectrum of diseases, from diabetes to depression. Each person’s collection of bacteria is unique, with no known “core” of species shared across all humans.

Among the patterns emerging from the data:

• How much of their microbial diversity participants shared with others depended greatly on how recently they had taken antibiotics. Those participants who had taken antibiotics within the last year tended to have less shared diversity.


• Alcohol imbibers tended to have greater microbial diversity than those who don’t drink alcohol at all.


• Spikes in microbiome populations seem to occur around holidays: in July, and in November through January.


• There is no single organism that is found in every person, but some are more common across the population than others.


• People who sleep more, and who exercise outdoors, have more diverse microbiomes.


• As seen in other studies, the elderly resemble infants in certain respects of their microbiomes.

“These patterns are certainly interesting, and we are hoping that the American Gut data provides other researchers a foundation to further study the effects of diet and lifestyle on the human microbiome,” says Knight, who was recently announced as a finalist in the Blavatnik Awards for Young Scientists program for his work on the microbiome.

“This isn’t a diagnostic tool to detect disease, but it may lead to the development of many tools that doctors can use to diagnose and treat a wide variety of diseases that are influenced by the microbiome.”

The American Gut data are the result of the work of a consortium of more than 90 researchers from 29 institutions. These researchers combined have published more than 800 peer-reviewed papers on the microbiome, and many of these researchers collaborated on the $173 million NIH-funded Human Microbiome Project.

The American Gut Project is an “open source” effort, meaning participants and researchers have access to the data gathered to help understand how diet and lifestyle may contribute to human health through the interaction of our microbiomes, cells and genes.

Most participants in the American Gut project donated $99 and requested that their microbiome be sequenced and analyzed. The project is currently the largest crowdfunded, citizen bioscience project ever launched.

“The thousands of participants who’ve joined the American Gut Project and made this extraordinary data set possible verifies the importance of citizen scientists in unwinding some of the most interesting and important questions of our time,” says Jeff Leach, co-founder of the American Gut Projects and founder of the Human Food Project. “Finding what makes us sick has never been more important to our growing global population.”

Most of the data for American Gut was sequenced by Knight’s lab at CU-Boulder. Participants received a run-down of what bacteria are in their sample, as well as comparisons with the rest of the American Gut Project, Human Microbiome Project and a few other populations.

Food and nutrition author Michael Pollan was among the first individuals to provide a sample for the project.

“Any researcher who is looking into the human microbiome will benefit from the American Gut data and the new processing pipeline we are releasing,” says Daniel McDonald, an interdisciplinary quantitative biology graduate student in Knight’s lab who has worked on the project since it began.

“Researchers will be able to frame their own data against the American Gut data for context or additional insight. The American Gut data are broader than any other known human microbiome dataset, with participants covering the full range of ages, BMIs and diet.”

Due to its success and the value of the data being collected, Knight expects the American Gut Project to continue and expand, with Australian Gut and British Gut projects currently in the works. The research team still needs more samples to reduce the signal-to-noise challenges of such a large dataset.

McDonald notes that it’s the people on the fringes of the data that help them the most: people with autoimmune diseases, teenagers, and those with unusual dietary habits. Getting more people to participate in the project will only strengthen the citizen-science data. A broader set of data would also give other researchers valuable information to help them design better tests and drugs for a wide variety of people.

Knight also is planning the release of a free online course offered through Coursera later this year for anyone wanting to learn more about the microbiome. The course will be titled, “Gut Check: Exploring your microbiome.”

Optimizing the microbes you have may be even more important than optimizing your lifestyle—although in many cases you may be able to optimize your microbes by optimizing your lifestyle.”

“Microbes may be the missing piece of the puzzle that make personalized medicine work,” says Knight, describing how the effects of drugs, including toxicity and efficacy, can depend on what microbes you have. “Optimizing the microbes you have may be even more important than optimizing your lifestyle—although in many cases you may be able to optimize your microbes by optimizing your lifestyle.”

The Human Microbiome Project and other microbiome projects worldwide laid an important foundation for understanding the trillions of microbes that inhabit the human body. Now, American Gut gives citizens an opportunity to participate and to compare the microbes in their guts to those in the guts of thousands of other people in the United States and around the world.

American Gut is a project built on the open-source and open-access principles of the Earth Microbiome Project. Its data are available for use for any purpose and are made available to the general public through the International Nucleotide Sequence Database Collaboration (INSDC).

The processing pipeline that converts the raw data into sequencing results is also available in a self-contained package that anyone can install and run. This emphasis on “reproducible computing” is a first for any major microbiome initiative. Find out more at: http://americangut.org.

At the University of Colorado BioFrontiers Institute, researchers from the life sciences, physical sciences, computer science and engineering work together to uncover new knowledge at the frontiers of science and partnering with industry to make their discoveries relevant. Learn more at http://biofrontiers.colorado.edu.

Emilia Costales is communications manager for the BioFrontiers Institute.