A complex evolution is happening within you, very rapidly, right now. Billions of individual bacteria, representing hundreds of species, are reproducing and living out their short lives in every human gut, all while helping digest food and influencing the health of their host.

While some may find this unsettling, Ben Good finds it fascinating – as a physics problem. The Stanford biophysicist sees the evolutionary behavior of these massive populations of organisms as similar to the behavior of gases or other materials with many interacting particles.

Ben Good | LiPo Ching / Stanford University

“Physicists have made enormous progress in developing tools for dealing with large systems of interacting components, so I'm captivated by this idea: What if we could understand evolution as well as we understand some of the physical processes happening in materials?” said Good, an assistant professor of applied physics in the School of Humanities and Sciences.

And if researchers can understand the evolution of these bacteria, they might be able to improve human health and develop treatments for a range of illnesses, since the gut microbiome is believed to influence not only digestion, but also the immune system and even brain functions.

Beyond test tubes

As a doctoral student at Harvard University, Good analyzed laboratory evolution experiments that grew populations of individual bacteria, such as E. coli, in test tubes. This was an effective way to understand the evolution of a single species in a laboratory setting, Good said, but it did not begin to touch what happens in more complicated communities.

A single person’s gut has hundreds of bacterial species interacting and evolving within it. At the same time, it can also be impacted by the invasion of external bacteria, which have been evolving in other people.

This is where a physics lens can help, Good believes.

“We have this saying in physics that there are only three sizes we should think about: one particle, two particles, and an infinite number of particles,” he said.

For gases, rather than trying to predict the position of a single particle over time, physicists instead investigate how the whole system responds using global variables like temperature or pressure. Microbiome researchers like Good are looking to see what comparable system-wide effects there are for the gut microbiome.

“These bacteria all have their own genomes. They don't necessarily care about each other; they don't necessarily care about us, and there are a lot of idiosyncratic interactions,” Good said. “Yet despite that, someone can be born and get colonized by this very complex bacteria community in a pretty reproducible way. To me, that suggests there must be some simpler rules underlying this process.”

The evolution inside and out

Each human’s gut is an ecosystem for bacteria, but it is not a closed system – and bacteria may jump from one person to another. Sometimes the “invading” bacteria are quickly overcome and do not become a significant part of their new ecosystem. Other times, they colonize the new host, causing a “strain replacement,” meaning they replace all the existing bacteria of the same species.

Strain replacement can be bad or good for the host, and currently, some experimental treatments seek to bring it about on purpose with a fecal microbiome transplant. This is a treatment that involves giving the good gut bacteria from one person to a person with a digestive condition to help recolonize their system.

Currently, this type of treatment mostly relies on guesswork to match a patient with a person who has an apparently healthy gut biome, but research like that from Good’s lab could one day help inform such treatments, making them more precise and effective.

Knowing more about how gut bacteria evolve could also help create nutritional solutions to some ailments since simply eating, or not eating, some foods can influence these organisms.

Good has been collaborating with other Stanford researchers on several projects related to understanding how this process works. One study with KC Huang, professor of bioengineering in the School of Engineering, and Justin Sonnenburg, professor of microbiology and immunology in the School of Medicine, involves using “genetic barcodes” on human gut bacteria in mice to track how the microorganisms evolve and move between individuals.

Another study, with David Relman, professor of microbiology and immunology in the School of Medicine, investigates this transference by studying people who live together in the same household. The researchers have one member of the household take an antibiotic, such as is normally given for a mild infection. Taking an antibiotic can decrease some of a person’s internal bacteria, and this could give “invading” bacteria an opportunity. The scientists then see if the antibiotic changes the taker’s susceptibility to being colonized by bacterial strains from their partner.

This type of research can provide insights to develop new treatments. It also presents an opportunity to learn more about evolution in general since gut bacteria evolve so quickly, Good said. He pointed out that 10 years of human life can be roughly equivalent to 10,000 generations for some bacteria.

“Evolution is all around us. It's happening all the time, not just on long timescales,” Good said. “It’s a big mystery in the field as to when evolution would prefer to import innovations from the outside versus evolving them locally, and I think the gut microbiome is a really great place to be thinking about that question.