Until recently, microbiology has been a science done largely in petri dishes, looking at a few million copies of one organism and asking simple questions trying to suss out how it’ll behave in the wider world. What does it eat? Does it breathe air like we do, or is it an anaerobe, to which oxygen means death? Now, however, there’s a radical new understanding sweeping the scientific world—and researchers are having to devise new tools to keep up.
Part of this revolution is the knowledge that we all play host to roughly a thousand different species of microbe, many of which are inherited shortly after birth in a mother’s milk. Passed down mother-to-child almost without fail for the past thousand generations, the genes of these microbes are practically as much a part of the human organism as our mitochondrial DNA. Although we’ve known about the human microbiome for some time, the knowledge of its guaranteed transmission across generations, and the implication that it’s essential for healthy human development, is relatively new.
|You have roughly as many microbial cells in your body right now as you do human cells, and more than 90% of the different protein-coding genes in your body are microbial genes, rather than human ones—which stands to reason; there’s only one species of human in you, but nearly a thousand species of microbe.
Image Credit: University of Michigan Health
Also relatively new is the widespread awareness that we have been playing fast and loose with this expanded genome. Antibiotics have been handed out willy-nilly practically since their invention, being used not just to prevent or cure illnesses, but to fatten up livestock and to enable animals to be kept in warehouses that would otherwise breed unmanageable disease. These techniques of “growth promotion” have led to the development of antibiotic resistance genes, which find their way into human populations through the food supply and other, more mysterious means—in part thanks to bacteria’s ability to trade useful genes with one another in a process called horizontal gene transfer.
These facts have contributed to the popularity of a different kind of microbiology, one much closer in practice to ecology than the single-strain-in-a-petri dish model that’s dominated since the advent of germ theory. We’re coming to understand that a microbe’s interactions with its environment and the other microbes around it may be far more important than its species; a microbe that’s ordinarily nonpathogenic might become problematic when deprived of a certain nutrient, or grow out of control if its competition for resources is eliminated by a course of antibiotics.
The most surprising new finding, however, is the recent discovery that we’ve been using methods which work fine for macroscopic ecology, but which have so little relevance at the microbial scale as to be useless. A recent study compared the genomes of 60 different strains of the same species—E. coli—and found that they have only 20% of their genes in common! Genetically speaking, you’re more similar to a banana than two of these E. coli strains are to one another.
So how can we talk about the interacting and evolving community of microbes around and within us, if the familiar unit of natural selection—the species—is useless? That’s the subject of new work by Mikhail Tikhonov, a researcher at Harvard’s Center of Mathematical Sciences & Applications, published last month in the American Physical Society’s journal Physical Review E.
Rather than treating variation within a species as slight perturbations from a prototypical organism that’s representative of the species at large, Tikhonov’s new model proposes starting from the assumption of complete disorder—abstaining from imposing any structure onto the ecosystem, and classifying organisms based on their unique functional characteristics. If two different microbes have the exact same set of genes, they can be lumped together, but if one has an extra metabolic pathway that lets it eat nutrients inaccessible to the other, they’re considered separate phenotypes.
The interplay among all these various phenotypes—whether they’re competing for food, cooperating, or assaulting one another through antibiotic production—is described in an interaction matrix, which has a row for every phenotype in the ecosystem. While this sounds impossible to construct, and hasn’t been done yet for a complex ecosystem like the one in your intestines, models of simpler systems with a few interacting phenotypes have been successful.
The beauty of “theoretical ecology without species” is that, if two organisms are similar enough that they really ought to be considered as one, they naturally will be, just by virtue of the way the interaction matrix is constructed and analyzed. Tikhonov’s proposed model is far more complex and computationally expensive than current paradigms, but may be necessary in the future if we want to truly understand what’s going on in our bodies and the world around us.
But whatever tools we end up using to combat the rapidly-arriving “antibiotic apocalypse”, it’s clear that the comparatively simple models which work so well for leopards or cows won’t do for Lactobacilli and Clostridia.