Human beings have developed to house lots of microorganisms called microbes. The human microbiome is the collection of millions of microbes that colonize the human body. Dr. Weinstock and his team at Washington University are applying the next generation of genomic sequencing technology to microbial genomics. The goal of this work is to analyze the genomes of these organisms, characterize the communities they form and measure how communities change in different health and disease states.
Q: Can you explain a little more about what human microbes are?
Microbes are everywhere in your body. They’re in your mouth. Your gut is just full of them. They help you digest food and they even make vitamins for you. Your body has evolved to house lots of microorganisms, without allowing them to destroy you. You actually have ten times more microbial cells in your body than human cells. You’re basically a big microbial community.
Q: So are you born with them?
Yes and no. You get some from your mother and you also acquire them throughout life. Microbes are in every nook and cranny of the world. They were here 3 billion years ago. We only showed up 100 million years ago so they’ve been here 30 times longer than we’ve been here. They’re responsible for minerals on the earth, for oxygen on the earth they’re these little machines that just convert things into chemistry. They can change the earth because there’s just so many of them.
Q: How do they work with the human body?
Your genome has 20,000 genes. You might have thousands of different species of bacteria living in you and each one of those has a few thousand genes. But you have so many of these species that you have 100 times more microbial genes than you have human genes. Those microbial genes are binding and changing things within you.
All of these microbial genes make up what is called your second genome or metagenome – a big genome made up of a bunch of little genomes. So you’re not just a human, you’re kind of a super organism because you’re a community of all these things that are with you your whole life.
Q: How does that affect the study of the Human Genome?
Once people started thinking about it that way, they realized we don’t really know anything about what these guys we’re carrying around with us are. Most of the time they’re doing an enormous amount for us but they’re not causing any problems, so we don’t even think about it. But we ought to understand what they’re doing so when things get out of whack (we’re able to understand) it may be because of changes in things (microbes) you’re carrying around with you.
Q: What’s an example of that?
Take plaque. Plaque is actually a community of microbes. They just bind to your teeth and normally don’t cause any problems. Plaque is happy to take what food passes by and offer some benefits to you. But if you eat lots of sugar, some of the bugs (plaque) can take it and grow like mad which can cause cavities. This is because the guys that overgrow secrete acid that causes damage to your teeth. A classic microbe is normal, stable and balanced. But if it gets out of balance, it can cause damage.
Q: What’s the Human Microbiome Project?
The Human Microbiome Project is going to sequence the second human genome, which are the genomes of all these organisms. We’re going to try to understand what’s going on in your microbiome. What does it do that makes it healthy? What is going wrong when it causes problems for you? How can we manipulate it and control it and make it better? It is the coolest project but it is so complicated because it’s not sequencing one genome. It’s sequencing thousands. Many of these organisms are so highly adapted to live with the other members of their community – the other species that are in us – that if you try to purify it in a test tube, it won’t grow because it needs things from the other organisms to survive. So you not only have to sequence the genomes of other microorganisms, you have to do it in the presence of other organisms.
Q: Are you able to distinguish what diseases are caused by microbiomes and which are caused by human genomes?
Since our (human) genomes are a little different from each other, we’re sequencing a thousand different human genomes to see where we’re all different. Our microbiomes may also be different. Men and women may have different biomes. We have to understand all of that – how the human genome interacts with microbial biomes, before we can absolutely distinguish those differences.
Q: Was the idea of researching microbiomes actualized in 1999 when the Human Genome Project began?
People have known about microbiomes for a long time. Generally they thought they were benign and that they don’t cause any problems. They thought that they’re just hitchhikers in us. So there wasn’t a lot of interest in them in 1999. Over the last five or ten years, people got more interested in them. After the Human Genome Project got started and we got good at DNA sequencing, we started sequencing a lot of individual bacteria. Then people began wondering if all that benign material wasn’t so benign. We wondered if there was something going on. And now with the sequencing power where it is, we’re able to discover a lot of interesting stuff going on.
We want to look at some valleys in the gastrointestinal tract, various skin and mouth diseases, ear infections, you name it. We want to go back and look at healthy people and people who have those diseases and look at their microbiomes. This will allow us to see if there are some kind of consistent changes in their microbiome communities that could account for or contribute to those diseases.
Q: Would someone living in St. Louis have a very different set of microbiomes living in them than say, someone in a small village in India?
We would think that diet would make a huge difference as well as hygiene. We would think that whether or not you brush your teeth, how often you take a shower, or the environment would make a big difference. That’s what we’re out to find out. Part of the human microbiome project is to answer those questions in a very precise way.
Q: Are there other sequencing centers throughout the world collecting samples from people of different nationalities?
There are human microbiome centers popping up all around the planet with most being in European countries. We just had the first meeting of the International Human Microbiome Consortium in Heidelberg, Germany. There were ten countries represented and we all compared notes. The International Consortium would like to answer questions about people from different nationalities and is figuring out how to systematically collect samples, analyze data, various things like that, so each individual project is able to leverage information to get the most out of this endeavor.