Robert Knight. Photo: James Duncan Davidson
The ancient Egyptians went to great pains to preserve the body for the afterlife. But there was one part of the body they didn’t bother with: the brain. Instead, they mashed it up, pulled it out of the nose and discarded it. Rob Knight wonders: Is there a part of our bodies that has just as much to do with who we are and how we feel that we haven’t yet paid much attention to? Yes, he says. And it’s our gut.
Knight’s lab studies our microbial landscape, which he explains is “critical to a whole range of what makes people different.” For example, if you’re one of those people who gets attacked by mosquitos while no one else around the campfire gets a single bite, it’s probably because of the microbes on your skin. Meanwhile, microbes in the gut determine whether painkillers are toxic to your liver, or if a certain type of medication will work for heart disease. Our microbes help us digest food, they shape our immune system, and some evidence suggests that they might even affect our behavior.
Knight sequences the DNA of the microbial communities in different parts of the body and has turned terabytes of data from 250 healthy volunteers into readable maps. He shows us one, which looks like an upside-down pyramid composed of multicolored dots. In the top left corner are green dots that represent the oral microbial community, to the right are the blue dots of the skin community, just below are the pink dots of the vaginal community, and far below are brown dots that represent the fecal community. “The different regions of the body have very different microbes. Microbes from one person’s gut and mouth can be as different as what you find in the coral reef and the desert prairie,” says Knight. “A few feet in your human body makes more difference than hundreds of miles on earth.”
Human beings share 99.9% of DNA in common. But two people might only have about 10% overlap in their microbes. It leads Knight to an interesting question: what comprises the human body? After all, we have 10 trillion human cells and 100 trillion microbial cells—and while we have 20,000 human genes, we have 2-20 million microbial genes. And while we leave traces of human DNA everywhere we go, we also leave traces of microbial DNA.
Our microbial communities are passed on during birth, when we’re coated in our mother’s vaginal microbes. This brings up an issue for children delivered via c-section, as the microbial communities passed to them look like skin, and this may be why they are at increased risk for allergies and asthma. “When my own daughter was delivered by emergency c-section, we took things into our own hands and made sure she was coated in vaginal microbes,” says Knight. “With one person, you don’t really have enough of a sample size. But she has not had a single ear infection.”
Knight shows a moving graph that charts a child developing its microbial landscape from day 1 through its second birthday. We see the four communities from the adult graph emerge—and then suddenly, there is a regression. Knight explains that this was when the child was given antibiotics for an ear infection. “This raises fundamental questions about what happens when we intervene at different stages in a child’s life,” he says. “It turns out that if you give children antibiotics in the first six months of life, they’re more likely to become obese later.”
Knight doesn’t mince words. “The three pounds of microbes that you carry around with you might be more important than every single gene you carry around in your genome,” he says. Microbes have been linked to heart disease, colon cancer and obesity in human beings and, in mice, to multiple sclerosis, depression and autism. But, of course, it’s hard to tell if this is correlation or causation. Knight shares with us a line of experimentation raising mice in a germ-free environment without microbes of their own. Then, microbes are introduced to see what happens. If these mice are introduced to microbes from obese mice, they get fatter than they do than when introduced to microbes from lean mice. They appear to put on weight because they eat more than a regular mouse. “The implication is that microbes can affect mammalian behavior,” says Knight.
So what happens when a microbe-free mouse is introduced to microbes from an obese human being? That’s right—it begins to eat more and gain weight. This suggests that the strategy of introducing microbes from one person to another could potentially be used as a medical intervention. Knight explains how his team is studying children in Malawi with a type of malnutrition called “kwashiorkor” that causes them to lose 30% of their body mass in a week. Could introducing new microbes help them recover?
To further research, Knight’s lab has launched American Gut, a crowd-sourced science project that 8,000 people are participating in so far. “It lets you claim a place yourself on this microbial map,” Knight says. But beyond that, it can help scientists explore the idea that microbes could help cure diseases.
It’s a fascinating area of research. To underline just how much potential it has, Knight introduces us to C.diff, a disease that leaves people suffering from diarrhea 20 times a day. Some patients don’t respond to antibiotics, and his lab conducted a study on people who’d had this condition for at least two years. By transplanting fecal microbes from healthy individuals into these patients, there was an immediate change in their gut community. The disease was cured—in as little as a single day. And it didn’t come back.
We’re not yet to the point where techniques like this can be used clinically—much research lies ahead. But Knight and his co-workers would like to help us get there.
“We need to develop a microbial GPS,” he says, “to understand where we are, where we want to go and what we need to do to get there.”