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Q&A: Gathering Diverse Microbiome Samples

Cofounders of a microbiome biobank speak with The Scientist about their new partnership with nonprofit OpenBiome and how to ethically work with donors.

Matthieu Groussin sits with three other people on stools in front of a low table, on which there are several bowls of food. Another person stands above Groussin spooning something into a bowl.
A black and white headshot of Katherine Irving
Katherine Irving

Katherine Irving is an intern at The Scientist. She studied creative writing, biology, and geology at Macalester College, where she honed her skills in journalism and podcast production and conducted research on dinosaur bones in Montana. Her work has previously been featured in Science.

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ABOVE: Mathieu Groussin (left) meets with the chief of a Hmong village in Thailand. © Global Microbiome Conservancy/C. Corzett

When microbiologist Mathilde Poyet and medical bioinformatician Mathieu Groussin first met as postdocs in Eric Alm’s microbiome lab at MIT in 2014, they realized two things. First, the lack of diversity in the microbiome data they were using made it nearly impossible for them to study anything but white people in industrialized communities, and therefore, the applicability of their work would be limited. Indeed, studies have found that data gathered from industrialized countries are unfit for creating therapies or microbiome-based treatments for use elsewhere. Second, they realized that they could do something about it.

Teaming up, the two embarked on a worldwide mission to recruit a greater variety of people to be represented in microbiome research. Groussin and Poyet have traveled to dozens of countries over the past six years to work with local scientists and communities, set up microbiome sample collections, and store them in a biobank. Their project became an international nonprofit, the Global Microbiome Conservancy (GMbC), which aims to capture the vast diversity of the human microbiome and use it to advance science and promote human health.

Now both medical faculty at the University of Kiel in Germany, Groussin and Poyet are handing the reins of GMbC over to OpenBiome, a Massachusetts-based nonprofit that has been principally known for collecting, screening, and distributing fecal microbiome samples for the treatment of colitis caused by an overgrowth of Clostridium difficile. The Scientist spoke with the two GMbC founders, (and occasionally their one-year-old, who made a few guest appearances) about their journey to build GMbC and what’s next for them after the merge.

The Scientist: How did the two of you meet?

Mathilde Poyet: We were postdocs, and we are working on our own project[s]: Mathieu is more the bioinformatics guy and I’m the wet lab person.

Mathieu Groussin: I was particularly interested in understanding how microbiomes actually changed during human evolution, but realized that it was impossible for me to address this question because about 90 percent of the human diversity was not represented in databases and resource collections. Mathilde was investigating the microbiology side of things and also realized that most of the diversity of bacteria that she could access was only coming from the same population. There was a huge lag in representation.

MP: We wanted to put underrepresented populations on the map. So we started this crazy project together, building this consortium.

TS: How exactly does GMbC work?

Mathilde Poyet wears gloves as she places vials into a circular blue container. A vial holder and prescription bottles sit next to the container on a protective pad covering the table.
Mathilde Poyet processes stool samples in the field in Malaysia.
© Global Microbiome Conservancy / Photo by C. Corzett

MP: We either contact or are contacted by scientists from many different countries that are interested in joining the consortium. Then we spend months building the project in the country. It means getting all the ethical permits, all the working permits, and everything. And then we travel over there, we meet with them, we train their local personnel—who are usually students—on how to process the sample, how to collect the sample, and we go all together to the field in very rural and isolated communities.

In most of the countries, we spend the first day in each community really trying to explain what’s the objective of the project, why it’s important for the microbiome science but also for them to be put on the map, to be represented in microbiome science. And we explain the kind of sample that we need from them. We try to spend some time with the population trying to build trust and a real relationship with them.

We process all the samples in the field—we travel with a dry shipper full of liquid nitrogen.

MG: The main scientific reason why we do that is because we want to preserve the original bacteria alive. If you take a stool sample and expose it to oxygen for a long time, the microbial diversity that is sensitive to oxygen dies, and so we . . . have the possibility to basically freeze it, but freeze it in a preservative way. So when we bring the samples back to the lab, we’re able to revive those microbes and culture them so that we can add them to our biobank of microbial isolates.

That’s really something that is key and very specific to our project. It’s not just about sequencing the DNA of those microbes; we are also doing all these efforts in order to actually isolate this microbial diversity so we can share it with the world and advance science with it. But some countries don’t have liquid nitrogen, so we have to travel to the neighbor country to get this liquid nitrogen. Sometimes . . . we have to transport it on the back of a horse for a very long time to access the remote communities, or even in a helicopter sometimes. It’s a challenge, but it’s worth it because that’s really what sets apart our project compared to others that are also very important, but focus primarily on sequencing the DNA.

TS: What does a biobank look like?

rows of labelled vials sit on shelves crusted over with ice.

The GMbC biobank of human-associated bacterial isolates
© Global Microbiome Conservancy / Photo by M. Poyet

MP: It’s not that huge, actually. We are using small vials. We make several outputs that we keep in -80° freezers. To give you an idea, to date we have one big freezer for all the samples, so that’s one thousand three hundred stool samples, and the official number of the strains is seven thousand bacterial strains.

There is also a bioinformatics component. We sequence the meta genomics and the systemic data from all the stool samples. And we also generate the whole genome sequence from each bacterial strain.

MG: Basically the biobank, on the computer side, links participants and their own health and lifestyle metadata up to the strain or bacterial genomic data. So we have all these connections between participant data, microbiome data, and bacterial isolate data that’s organized like any standard biobank right now.

TS: What had been the response of the research community? Are people excited—have they been wanting to contribute or use your data?

MG: The response has been great. More and more people are aware of the project and actually contact us to ask to be part of it, either because they want to be represented or because they have a scientific collaboration in mind that could be used to collect samples among populations in their country.

We also have an interesting and exciting paper that came out in Cell where we were able to find out that microbial genomes were actually responding to the industrialization of the lifestyle of their host. So it’s not just about microbial species that change from a nonindustrialized to an industrialized population, it’s also the bacterial genome[s] themselves that respond to these changes. In particular, they’re doing so through increased frequency of exchange of genes between different bacterial species. And so that was a very novel insight about how actually hosts’ lifestyle profoundly impact[s] the microbiome.

TS: How did your merger with OpenBiome come about?

MP: I guess it started because we realized that we’d reached a plateau. For [six] years it was mostly Mathieu and I doing everything from administrative work, to traveling and biobanking, to analyzing data. . . . We are scientists, we are researchers, so we wanted to get back to doing research. And also we’ve been contacted more by more people that want to join the consortium. And also personal reasons—we had a baby so we cannot travel as much.

We needed to find a way to reach the next level. And OpenBiome is coming from Eric [Alm’s] lab as well. So it was almost an internal conversation, actually. Everything makes sense because they have the lab, they have the people, they have the team. And we have the same the same vision for the future of the microbiome, how it’s important to do science ethically, equitably. It’s finally happening, and we are pretty excited about that.

Mathilde Poyet pipettes something into a vial at a lab station in the foreground as another scientist looks on.
A scientist at the National Reference Laboratory in Kigali, Rwanda, reviews bacterial DNA extraction protocols with Mathilde Poyet. 
© Global Microbiome Conservancy / Photo by C. Corzett

MG: One very critical aspect of the GMbC is ethics. When Mathilde and I started the project, we realized that there was a great deal of very important ethical issues surrounding the scientific work with underrepresented and sometimes Indigenous communities that had been abused in the past by the scientific community. And so we really wanted to protect as much as we could the interest of the participants in the research. We had this vision of building a nonprofit initiative that would totally protect the interests of participants, and the way we did it was by convincing everyone involved to leave the ownership of the samples to the participants so that samples could not be exploited and used for for-profit activities in the future. So that’s why, from an ethical standpoint, we are going to remain involved in the future of the GMbC program and OpenBiome by being the cochairs of the science and ethics advisory board. We have these topics really at heart, and we want to make sure it will remain that way if in the future the model changes so that we can also have possibilities to advance therapeutics, then it’s always done in a way that again shares benefits and protects the interests of participants.

TS: What would you say has been the most rewarding part of working on this project?

MG: I think I think we grew quite tremendously, Mathilde and myself, from a human side and we learned so much about different cultures, different diets, different religions, religious practices, different cultural habits—all of those different things that actually matter and impact our microbiome as well, which is which is at the core of our own scientific curiosity. We also created friendships all over the world. And eventually, what we really care about is to have a positive impact and influence on local scientists and local communities; we hope they richly gain from our collaboration, and that’s why we continue being involved in trainings, capacity buildings, collaborations, and providing local collaborators with data and knowledge that we have.

TS: Off of that, what do you hope that the field of microbiome research looks like in ten to twenty years?

MG: I think we are going towards personalized medicine in different medical fields, from cancer to immune disease, and the microbiome will be part of that enterprise as well. And personalized medicine can be at the level of individual, but it also needs to be at the level of populations which have very different characteristics from one country to another, or from one setting to another. This will be particularly relevant in the context of global urbanization and industrialization, as the UN predicts that 70 percent of the worldwide population will be urban by 2050. That means that a lot of populations around the world that are currently living in remote rural settings will transition very fast towards new lifestyles that will dramatically impact their health, their microbiome, and will contribute to the rise of microbiome-associated chronic disease. And so this is why there is a strong need in including all these populations right now to understand the specifics of their microbiome, so that we can then better understand and develop interventions that will have a positive impact on them in the future.

Editor’s note: This interview has been edited for brevity.

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