You Are What You Eat, And What You Eat is Millions of Microbes
Poop is nothing short of a scientific miracle. It helps researchers understand the diets of dinosaurs, trace the spread of ancient disease and recognize parasitic infection. Fresh human feces also provide a direct window into our guts and the billions of microscopic critters therein, which help digest our food, protect us against disease and even influence our moods.
That was the idea that fueled Rob Knight, one of the founding fathers of gut microbiome research, to start the American Gut Project in 2012. Knight used the crowdfunding platform FundRazr to coax more than 9,000 volunteers into first donating money, and then sending samples of their poop through the mail. A team of researchers probed these samples for bacterial DNA to create the first census of the 40 trillion or so bacteria that call our guts their home.
What he learned was revealing. But no matter how informative, illuminating and downright cool poop was, there was still something missing: Where do all those trillions of bacteria come from? It turns out that, for the most part, we’re voluntarily putting them in our mouths around three times a day. “You get an ongoing input of microbes from your environment—microbes you eat on food itself,” says Knight, who directs of the Center for Microbiome Innovation at the University of California at San Diego.
One of the mysteries sparked by the American Gut Project was why two people who claimed to follow the same diet could have such different communities of gut microbes. For the study, volunteers had self-reported their diets, with the vast majority following omnivorous diets, and less than 3 percent each identifying as "vegetarian" or "vegan." When researchers crunched the numbers, however, they found no discernible correlations between gut communities and those with seemingly similar diets.
“Diet categories were completely useless and didn’t correlate with the microbiome communities at all,” says Knight.
In other words, the bacteria in poop were telling a different dietary story than the people making that poop. “You can be a vegan who mostly eats kale, or you can be a vegan who mostly eats fries,” Knight explains. “Those have totally different consequences for your microbiome.” Anyone can claim to be a die-hard adherent to the Paleo Diet, it seems, but the data suggested that the microbiome remembers all those midnight ice cream transgressions.
Knight realized that the results of the American Gut Project were missing something crucial: A deeper dive into the food we eat. Filling that gap would mean analyzing all the food going in, and seeing how it correlated with the patterns in what comes out. But while collecting poop was, in some sense, straightforward—each person "submits a sample" in the same way—tallying up all the many foods people eat would be a lot more ambitious.
Every time you ingest, you change the interior landscape of you. Because the bulk of bacteria in the microbiome live in the gut, when we feed ourselves, we feed them too. The chemistry of what we eat, be it fries or kale, alters the chemical landscape of the gut, making it more cozy for some and less hospitable for others.
It gets livelier. Because microbes are everywhere—on the table, in the air, on the surface of the muffin you left out on the counter—you’re also adding new microbes to the mix. Some stroll through your body like polite tourists. Others stick around and interact with the locals. Every bite has the potential to alter the microbiome, and subsequently human health. But researchers have yet to figure out how.
That’s because, until now, we didn’t have the platform to embark on the massive endeavor of collecting and analyzing food samples from around the world. Thanks to the American Gut Project, Knight and his team aren't starting from scratch. Initially, the researchers plan to collect 1,000 samples from every brick of the familiar food pyramid, and then they’ll open it for the public to submit whatever foods they’re curious about.
Along with Knight, the food microbiome project is led by microbiologists Rachel Dutton, who uses cheese as a model system to understand microbial communities and fermentation, and Pieter Dorrestein, who studies the chemistry of biological interactions between microbes, both at the Center for Microbiome Innovation. They're aiming to launch this crowd-sourced initiative before the end of the year.
“We know about calorie count, and about different food groups, but the whole world of the molecules and the microbes in our food is a black box,” says Julia Gauglitz, a post-doctoral researcher at the center who will direct the project. As the old adage goes, “we are what we eat,” she says. And yet, when you get down to the microscopic level, “we know very little about what we’re consuming.”
The other “black box” researchers want to investigate is food's chemical composition. It turns out there’s a whole lot more than what’s listed on the Nutrition Facts label: With conventional techniques, only fats, sugars and vitamins can be measured, “but that’s only a small fraction of the total weight of food,” Dorrestein says. We could be overlooking novel antioxidants, cancer-fighting compounds or even stowaway antibiotics.
By using mass spectrometers—basically fancy scales that are precise enough to weigh individual molecules—Dorrestein can deduce the chemical composition of food at a level never before achieved. As the food samples roll in, Gauglitz will be waiting in the lab. She’ll take, say, a granola bar, extract all of the genetic material from the microbes colonizing it, and then use DNA sequencing to figure out the critters' identities.
She’ll then run a bite of that granola bar through the mass spectrometer to tease apart every single molecule that it’s made of. In the end, she’ll be left with a very, very detailed granola bar recipe. Those molecules make up the landscape where food microbes live, and likely influence who’s there and what they do.
I asked Gauglitz how she will distinguish between the chemical composition of the microbes living on the granola bar and the chemicals made by the microbes. “I would shift your thinking a little bit,” Gauglitz says, her voice growing philosophical. “What is intrinsically in the granola bar are also microbial metabolites.” Put another way, the granola bar is the microbes.
Everything we eat is the cumulative product of the chemistry and microbes in the soil where it was grown, the factory where it was processed, and whatever you touched right before you ate it. Why is that important? Ultimately, the team hopes, demystifying the microbial patterns in our food will help us better engineer our diets to improve our health and ward off disease.
Knight draws a historical parallel to the discovery of essential nutrients. In the last century, researchers figured out that industrially processed foods had become nutrient-depleted. By artificially adding vitamins and minerals back in, deficiency diseases like rickets and beriberi were largely eliminated from the Western world. Similarly, understanding the health effects of the microbiome could allow us to engineer those missing microbes back into our meals.
“It’s fairly likely that our modern lifestyles are stripping out a whole lot of live microbes that we need to maintain health,” says Knight. “Getting an understanding of that could be as important as the understanding that vitamin C is necessary and making sure that everyone got enough of it.”
The team has already picked out 1,000 foods for their initial survey, including staples like bread and cheese. “We want to include raw food ingredients, any kind of fruit or vegetable, meats, snacks, baby food,” Gauglitz says. But they also want to compare microbial communities in foods produced by organic and conventional farming, as well as look deeper into products that rely on microbial fermentation, like coffee, chocolate and sausage.
The project could also solve some of the medical mysteries raised by the previous microbiome research. For example, some of the tests in the American Gut Project sifted through each fecal sample for trace amounts of antibiotics. Strangely, of the people who had detectable antibiotics in their samples, nearly half of them had reported taking no antibiotics in the past year.
Dorrestein believes these are second-hand antibiotics we absorb from the food we eat, additives or things left over from livestock feed. This is worrisome, because their presence could lead to the spread antibiotic-resistant bacteria. By teasing apart the chemistry of each sample, the team will be able to figure out if he’s right, and start figuring out what these leftover drugs could be doing to our guts.
Appreciation for the power of the microbiome is growing, thanks in part to initiatives like the American Gut Project and books like Ed Yong's I Contain Multitudes. There’s even a burgeoning field dedicated to the microbiome of the built environment and how our microscopic roommates living in the air and on inanimate objects interact with us. Humans aren’t unique in this regard; studies of microbiomes in critters from coral reefs to honeybees show that the health of any organism is intimately tied to the microbes that call it home.
As a result, microbes are starting to turn around their reputation. No longer are they merely menaces in a germ-averse culture. Within the past decade, “nutritionists recognized the importance for gut health and human health to have healthy microbes in our large and small intestines,” says Helena Pachón, a senior nutrition scientist at Emory University who is not involved in the food microbiome project.
Pachón points out that, today, those historic deficiency diseases that Knight refers to have been surpassed by 21st century afflictions like obesity, diabetes and heart disease. “There’s a term called ‘globesity’,” says Pachón. “The potential that microbes could have something to do with this is completely unexplored, and it could be that they’re highly related.”
Knight agrees. “It would be amazing to come up with a way through food to eliminate them in just the same way that those chronic diseases a century ago have been,” he says. To do so, "we need the help of thousands of people to pull it all together.”