The Nanotech View of the Microbiome

February 12, 2015

Alan Brown, writer and editor for the Kavli Foundation, edited this roundtable for Live Science's Expert Voices: Op-Ed & Insights.

Microbiomes — communities of microorganisms — exist nearly everywhere, from the soil and the sediment under oceans, rivers and lakes to the landscapes of the human body. They are ubiquitous, mediating the interactions of plants and animals with their environments, and yet we know very little about them. 

The Kavli Spotlight, a series of roundtables and live Internet events, has previously covered how the human microbiome influences brain development, and how the study of natural microbiomes drives the search for extraterrestrial life. Our latest roundtable looks at the role of nanoscience and nanotechnology in revealing microbiome communities.

The challenge is significant. Within only a few grams of soil or ocean sediment, rich and complex ecosystems exist that contain hundreds of thousands of different microbial species. Scientists cannot yet grow the vast majority of these single-celled organisms in a lab, and so they are immune to classification by conventional technologies. 

Nanoscience  may be able to help tease apart how the members of natural microbiomes interact with one another. To discuss this, the Kavli Foundation has invited two leaders in the field:

Eoin Brodie is staff scientist in the Ecology Department at the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory, and adjunct assistant professor in the Department of Environmental Science, Policy and Management at the University of California, Berkeley. He has pioneered technologies for accurately measuring microbiome community dynamics.

Jack Gilbert is principal investigator in the Biosciences Division at the DOE's Argonne National Laboratory and associate professor in the Department of Ecology and Evolution at the University of Chicago. He has studied the microbiomes that exist within hospitals and is working on ways to use bacteria-embedded nanostructures to rebuild infant microbiomes.

Below is an edited transcript of their discussion. The participants have also been provided the opportunity to amend or edit their remarks.

The Kavli Foundation: What makes a microbiome a microbiome? Is it only about size, or does it require a certain complexity?

Jack Gilbert uses next-generation sequencing devices to understand to classify and understand the functional role of bacterial communities. Through the Earth Microbiome Project, he seeks to characterize the microbial diversity of our planet. (Image credit: Argonne National Laboratory)

Jack A. Gilbert: A microbiome is a community of single-celled microbes. It could include bacteria, fungi, protozoa, algae and viruses. It's a little community whose members are interacting with each other. It can be anything, from ten different species to 1,000 species to 200,000 species. 

Eoin Brodie: Consider this analogy: Think of all the different things you might find in a tropical forest. You've got different types of trees and animals and insects. All these things have evolved to work together to form some sort of stable system, in many cases, an ecosystem. So a microbiome is the microbial version of that forest ecosystem. Individually, each different species provides different functions that, together, are essential for the stability and activity of the system. [Body Bugs: 5 Surprising Facts About Your Microbiome Countdown]

TKF: Are there properties that emerge when microbiomes reach a certain size or level of complexity? Are they different from the properties of individual microbes?

J.G.: There are. This is an area of ongoing research, though we can start by looking at how ecological theory plays out in larger organisms. That helps us interpret and predict what microbiomes might do as they grow in complexity.

As complexity increases, we see more interconnections in the system. Think of it like a food web. If it combines multiple insects, trees, plants, and other things, it is potentially more stable than if it has only a single insect and a single tree. The more participants, the more interactions, and these interactions trigger still more interactions. Together, they regulate the abundance of specific types of organisms. Nothing takes over, they all share resources.

At exactly what point an ecosystem becomes stable or resilient is less clear. Macro-ecological theory suggests that when there are more connections, you build in redundancy. This makes the system more robust and resistant to disturbance, though there is a sweet-spot that may be hard to define. Larger ecosystems may have several organisms doing the same thing, though not necessarily at the same time or in the same place. But those organisms could step in when another organism performing that function cannot do so. 

J.G.: This is an interesting point. The very definition of a highly robust community or ecosystem is inherent flexibility. It's like a reed bending in a stream, flexing with changes in stress and pressure. Redundancy is part of that. There may be 20 organisms that produce methane, which is then used by other organisms. The members of that methane-producing community will respond differently to changing conditions. One might grow better at higher temperatures, another if temperatures drop. But the fundamental function of that assemblage producing methane, hasn't changed. 

TKF: Microbiomes are clearly complex and interconnected. They can have hundreds of thousands of different species. How do we begin to understand something like that? What's the current state of the art?

J.G.: There are multiple states of the art. 

E.B.: It's true. For example, we can only grow between 0.001 percent and maybe 10 percent of the microbes we find. For some systems, like the human gut, we are getting better because we know more about them. 

In soils, we're not very good. That's because it's very hard to predict what these microbes need to grow. They may have unusual nutritional requirements are, or need other organisms to grow. It almost impossible to grow them in a pure culture. 

One window into their function has been things that Jack has pioneered, using metagenomics and sequencing technologies that were developed for human genome sequencing. We can apply those technologies to these incredibly complicated microbial communities. 

So we take this community apart, just like an enormous jigsaw puzzle, and break it up into tiny, tiny molecular pieces that we can measure with sequencing machines. The real challenge, however, is putting those pieces back together again in a way that tells you something about the whole community. So, that's one approach. 

Another approach involves imaging organisms. You can see them using visible light or other wavelengths, identify their shapes, and learn about the chemistry associated with them. We have done that in some very simple artificial microbial communities we’ve grown in the lab. The challenge is finding ways to apply these technologies to increasingly more complicated systems.

J.G.: You know, you can put "omics" at the end of anything and get a new tool out of it. Genomics measures genes. Transcriptomics covers RNA transcribed from genes. Proteinomics looks at proteins folded by transcribed RNA. Metabolomics analyzes the chemicals and metabolites mediated by those proteins. There's a whole slew of them, and that means we have a lot of tools that can interrogate the components of the system. [The Hunt for Alien Extremophiles is Taking Off (Kavli Q+A) ]

One of our key challenges is to integrate all this information. Eoin's been developing some techniques to attack this problem by compiling this data into an interoperable data framework. It's all very well having a genome, a transcriptome, a metabolome — but pulling those together and creating knowledge out of the chaos can sometimes be an über challenge.