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Exploring the human biome
Perspective// Posted by: Christine Mason / 12 Apr 2016
Exploring the human biome

San Francisco-based Second Genome works with the human biome, studying the vast population of microorganisms which—though they’re not human—are integral parts of our being (and surround our beings as well, in a “microbiotic cloud”). ENTER (Jeff Greenwald) discusses microbiomes and personhood with two members of the group: Todd DeSantis and Adam Altrichter.

DeSantis is Second Genome’s co-founder and Senior Director of Bioinformatics. He has worked in biometrics at Lawrence Berkeley National Laboratory and with the NIH Human Microbiome Project. He also serves as the chief architect of Greengenes™, an international project dedicated to cataloguing global microbial diversity. Altrichter, who joined Second Genome in 2014, began his work studying microbial ecology in Antarctica. He’s since moved north to consider the connections between human activity, architectural design and the distribution of bacteria in everyday living and working spaces.

Todd DeSantis Adam Altrichter

Todd DeSantis

Adam Altrichter

ENTER: Let’s start with a refresher. What exactly is the human microbiome?

Todd Z. DeSantis: I use it to refer to the community of microorganisms that live together within and upon the human body. What surprises most people I meet is when I tell them “we have ten times as many non-human cells in our ‘biosuit’ than human cells.”

ENTER: That’s an interesting term. Can you define it?

TZD: I wear a “biosuit” of human and microbial cells—and the blend matters. It really makes one think about the definition of “I.” Most of my microbial cells are smaller than my human cells, and most are limited to the gastrointestinal tract, so the human cells are still really important for health. That’s why our company studies the communication between microbes and human cells.

ENTER: What percentage of you, me or our labradoodle is actually microbial?

TZD: By weight, it might be about five percent. The compelling aspect is that, when it comes to the technical skills known by a cell, a human cell is well-equipped; it can carry out many functions. Any individual microbial cell is less skilled. But, when you consider a community of microbes made up of hundreds or even thousands of different species, then the diversity of functions encoded in the microbes is even greater than the diversity encoded in the human cells. They can digest materials we cannot, they can create complex molecules that we cannot. They can wage microbial war in ways that our human cells cannot.

ENTER: What’s the actual process for figuring out what’s going on inside of our bodies?

We're learning what molecules are made by the microbes living inside of us, and how those molecules act upon human tissues.

TZD: As an example, we take intestinal biopsies of healthy and diseased individuals, then examine their DNA (to determine functional potential) and RNA (to determine functions turned-on at the moment). We use a variety of laboratory tools (proprietary as well as non-proprietary) and big-data software tools enabled by cloud-scale computing. Since a biopsy contains both human and microbial cells, we observe what happens when the cells are living next to each other. Then we compare what we find between the diseased and healthy individuals.

ENTER: How does this relate to what’s been called our “microbiotic cloud?”

TZD: This term refers mostly to the microbes that humans and animals leave behind in the air we move through—microbes launched from our skin, exhalations and saliva, maybe flatulence, too.

ENTER: Is the microbiome inseparable from who we are?

TZD: I’m a big believer in free will, but we must acknowledge that there are constant silent influences upon our mental state. Out in Denmark, at the University of Copenhagen, a team is developing ways to test the relationships between diet, gut microbes, anxiety and memory.

Microbiome

In one experiment I’m aware of, mice are placed in a shallow pool 15cm (about 7”) deep. A clear Plexiglas platform is placed in one region of the pool; they can climb onboard and be only 1cm deep (which they much prefer). You can put the mouse in the pool every day, and see how well they remember where the platform was. After feeding them different diets which cause changes in the microbial communities in their gut, they test how quickly a mouse can recall where that shallow ledge is located. In mice with feces overgrown in the “S24-7” family, better memory performance was observed. A high fat diet depressed the S24-7 family, and reduced memory. I’m looking forward to seeing follow-up studies in this area.

ENTER: What do you mean by the “S24-7” family?

TZD: These are bacteria that have never been studied in captivity (in other words, they’re not able to be cultured). We know where they’ve lived by sequencing DNA found in feces. They’re sorta like those elements way down at the bottom of the periodic table; you can’t get them into a test tube, but you can observe indirect evidence of their existence. Discovering ways to culture these and other elusive bacteria is part of ongoing research. The S24-7’s are most similar (by DNA matching) to the parabacteroides, bacteria a group able to withstand even high-levels of harsh bile.

ENTER: Do people from different parts of the world have different microbiomes?

TZD: Significant differences have been found in infants depending on their region and diet—two influences which are often conflated.

ENTER: What can we learn by studying the human microbiome?

TZD: We’re learning what molecules are made by the microbes living inside of us, and how those molecules act upon human tissues. We ask, “What happens to human tissues when the molecules are over- or under- produced?”.The observations lead us to drug discovery. In other words, we are looking not just for bacteria that assist in health (probiotics) but exactly how they exert their help, so that we can create specific therapeutics.

ENTER: Are different personality types—or even mental conditions—reflected in our microbiome?

Genome

TZD: Well… Do you think obesity and behavior are related? One famous experiment showcasing the influence of gut microbes was done at the University of Washington in St. Louis. You see, normal mice are fairly lean, muscular, active animals. There are some, though, missing a gene for leptin. When mice are missing leptin they overeat uncontrollably, store the excess calories as fat, and become obese.

Those leptin-deficient mice have the same types of bacteria in their colons as normal mice—but the relative proportion of the different types of bacteria are drastically altered in the obese mice. For example, the lean mice have much higher populations of a group called “Bacteroidetes.”

Now, here’s the exciting part of the experiment: Let’s say you take a scoop of the gut bacteria from an obese mouse, and add it into a clean digestive tract of a normal mouse. That normal mouse doesn’t eat any more food than usual—but it begins accumulating unhealthy body fat within two weeks. On the other hand, if you place lean bacteria into a recipient mouse, the mouse lives a lean life.

This outcome—which shows that you can affect health simply by changing the community of bacteria in the gut—has triggered US, Asian and European research funds toward searching for links between gut bacteria and difficult-to-cure diseases such as obesity, diabetes, ulcerative colitis, Crohn’s, autism, allergies, etc.

We like to imagine ourselves as self-reliant individuals. Our growing understanding of our reliance on these microbial partners is a direct challenge to that notion of selfhood.

ENTER: Adam, let’s turn to you for the next couple of questions. How does information about the microbiome challenge our ideas about personhood?

ADAM ALTRICHTER: I think we like to imagine ourselves as self-reliant individuals. Our growing understanding of our reliance on these microbial partners is a direct challenge to that notion of selfhood. We can’t operate as humans without these organisms. Some of the analogies for the microbiome, in fact, liken it to a newly discovered organ in our bodies.

Perhaps even more challenging is the realization that we’re constantly releasing bits of that microbial organ into the environment and impacting the individuals (and their microbiomes) around us. If one way to define ourselves is through our genetic makeup—and if the microbiome represents a part of our genetic composition that varies and gets exchanged with our neighbors—how different are we, really, from the person sitting next to us?

ENTER: Is the microbiome is a mindless haze of organisms, or does it have a sort of cognition separate from ours as people?

AA: The microbiome certainly has the ability to create, modify, and accumulate genetic information, if that’s a sort of cognition. The organisms respond to changes in their environment, cues from each other, or threats from phage infection. As a collection, the microbiome has a toolbox of genes that’s very deep and very adaptable. I think it’s this diversity and mutability that gives it some semblance of autonomy with capabilities distinct from our human genome.

ENTER: Todd, would any attempt to replicate a person’s consciousness—I’m thinking about the Singularity—have to include a microbiotic cloud?

TZD: It wouldn’t hurt. I guess if I was to be preserved for the future, I’d want to make sure my microbial community could be preserved and reconstituted with me. Or could I elect to use Jason Witten’s?

ENTER: Do you feel the awareness of our microbiome enhances or decreases our personhood?

TZD: Hmmm. If I want to improve who I am, I can get more degrees, learn from my mistakes, do pull-ups frequently—and potentially change my microbial community. So, being aware of the microbiome makes my list of options greater! I don’t think it takes away from our personhood.

Or maybe my microbes are making me answer that way so as not to alert the plebe cells about the identity of their true puppet-master.