Last month, the world’s largest study of the bacteria that reside in and on us, the American Gut Project (AGP), came out.
Early results of the ongoing survey suggest that the number of different plant types one eats increases the diversity of the microbiome, while antibiotics tend to decrease that diversity, which is associated with good health. Alcohol use is also linked to a more diverse microbiome. And those suffering from mental illness seem to have more in common in their gut bacteria than those in the mentally healthy group.
The study of our genome was actually the catalyzing force in the exploration of the microbiome. Like the space race in the ’60s, the nearly $3 billion spent on the Human Genome Project helped create the sequencer technology that made study of the microbiome affordable for everyday people.
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“In just the last 15 years the cost has dropped by about a million-fold,” Dr. Rob Knight, who co-founded the American Gut Project in 2012, told The Daily Beast. “You probably wouldn’t spend $100 million dollars to find out what’s in your gut, but you might pay $100.”
AGP builds upon the work of the Human Microbiome Project (which finished in 2013) after testing 300 very healthy volunteers in the United States. While the Microbiome Project—which had an extensive health screening protocol—offers some guidance on what a healthy gut might look like, it misses the bacteria more represented in less than fully healthy guts. Also it’s a very small sample. (Perhaps like looking at the 300 New Yorkers who aren’t neurotic in a city of 8 million.)
Though it’s called the American Gut Project it’s a global effort. The AGP’s database features 15,000-plus samples from over 11,000 individuals in 42 countries, and it’s growing every day. Unlike most studies, which are rigorously controlled with small sample sizes and proprietary data, AGP’s approach is broadly inclusive and employs an open-access platform.
It’s crowdsourced and crowdfunded, allowing anyone to participate for a $99 fee that covers the sample’s processing. Participants fill out a questionnaire and when their results return can view them in isolation and in context of the entire database. Still, there are far more samples of people with Western than non-Western diets, and substantially more women and older people (more capable/willing to pay the fee), as well as more obese individuals (PDF).
“We wanted to set up a structure where everyone could participate,” Knight said. “We thought it was really important that the people participating be contributing to an open resource that any educator, researcher, physician, patient—hell, anyone who’s just interested in what microbiomes look like—could go to that free and open resource and download not just their own data, but the data everyone contributed.”
Unlike organ transplants, these carefully screened healthy biome-grafts have experienced a high success rate (over 90 percent) allowing the patient to return to their former life as if nothing happened. There’s already an Athletic Microbiome Project looking for connections in the guts of elite bicyclists and runners. But there can be side effects. There have been reports of people becoming obese after a Fecal Matter Transplant (FMT), and even an anecdotal case of a man with alopecia since childhood suddenly growing hair.
Studies are already underway linking the microbiome to chronic inflammatory and immune system diseases such as multiple sclerosis. In St. Louis, Washington University Dr. Jeff Gordon is exploring the link between our gut bacteria and weight, including a groundbreaking Malawi twins study that linked malnutrition to the gut and not food intake. A new study was even able to lengthen fruit fly lives by 40 percent through a combination of probiotics and the Indian herbal supplement Triphala.
Two years ago on her birthday, my wife and I took part in the project because it seemed new, cool, and strange. I’d discovered AGP in the process of doing a story on fecal transplants. Antibiotic-resistant bacteria have given rise to a flux of debilitating gastrointestinal diseases which limit the ability of sufferers to leave their house. However some have found a cure through reintroducing the bacteria found in a healthy person’s shit, proving what they say about “one man’s trash.”
Having been married for a half-dozen years at that point, we expected a lot more similarity in our gut bacteria. Instead, our guts seemed like polar opposites. My gut was rich in the gram-positive firmicutes bacteria to the near exclusion of anything else, while my wife’s gut was more than 80 percent gram-negative proteobacteria with hardly any firmicutes at all.
We shared meals and a living space, so this seemed strange. But it’s a testament to how little we still know about how our biomes are transmitted and conveyed.
“On average you’re probably more similar to your wife than an unrelated person in the American gut population. There’s just a tremendous hyper-variablilty at the level of those nature taxa between people,” Knight said. “Even if you sampled yourself on a whole lot of consecutive days you would see variation in yourself one day to the next.
“Although one thing we’ve found is that people who live together think they eat very similar diets but it’s not really true,” he added. “Just because the same stuff is available to you doesn’t necessarily mean you put the same amount on your plate.”
This natural variability conspired with science’s still limited understanding of the microbiome to leave my wife and I struggling with how to apply our new knowledge. Though she’s suffered from gastrointestinal distress and dysbiosis, her results didn’t necessarily yield any clear treatments. Beyond that, changing your microbiome appears to mostly be a slow, incremental affair requiring patience and healthy skepticism. Nonetheless, I began mixing the prebiotic fiber Inulin with my stevia-sweetened iced tea, based on some promising research.
Knight notes that while probiotics can work on people suffering serious intestinal trauma, that doesn’t say anything for less debilitating situations like my wife.
“Just because the particular protobiotic is good for curing that particular disease doesn’t mean at all that it will improve your health as a baseline,” Knight says. “Chemotherapy helps you out with cancer but that definitely doesn’t mean you should take Methotrexate all the time to improve your health.”
That doesn’t mean a biome can’t change dramatically, particularly after major surgery. That news comes courtesy, Dr. Larry Smarr, a colleague from University of California-San Diego, where Knight’s lab is situated. Dr. Smarr sampled himself regularly in advance of and after undergoing colorectal surgery. The before/after change was more dramatic than anything they’d seen before, even from extreme diets.
“If Larry hadn’t sampled himself every single day it would’ve been impossible to see the dramatic change that we saw after surgery. A typical longitudinal study… you’re going to miss almost everything that is interesting that’s going on in the microbiome if you don’t sample it frequently,” Knight says. “It would be kind of like measuring the water level at the beach once every six months and knowing nothing about the tides.”
Knight points to how much we don’t know about our microbiome and how it responds to the trauma of medical procedures or courses of antibiotics. Indeed, the very lack of a consistent story is one of the themes.
“What we have right now is a tremendous knowledge gap,” Knight said. “We have seen the same antibiotics and same dose has a completely different impact on the microbiomes of different people, the direction of changes and how long it takes to recover.”
In short, the AGP proves that there’s tremendous variability in our guts, much like the different climes on our planet. You wouldn’t expect the Inuit to have the same behavior and survival strategies as Australian bushmen, and our individual gut flora are at least as disparate. (It’s also why the AGP’s broad, open-ended, world-spanning approach is so appropriate.)
Not only do our gut bacteria grow less diverse as we age (outside childhood), but they’ve quantified it. They’ve run a regression analysis that can guess your age within a few years based on your gut bacteria.
“If you want to know your age it’s a lot easier to look at your driver’s license,” Knight admits. “But on the other hand there’s an important question about when you look at the regression results… can we tell if people are aging prematurely or aging well based on their microbiome?”
The field’s come a long way in the last dozen years and knowledge is growing quickly. Knight notes that there are centenarians around the world who have very different diets, implying that achieving one’s best biology self may have multiple approaches. Given evolution’s “competitive nature” perhaps the best model for all these different microbiome gambits lies in the very embodiment of human striving: Wall Street.
“The kinds of measures we have now are mostly from ecology,” Knight says. “It’s entirely possible we should be looking at econometrics to handle this very complicated multivariate time-series. That’s what really needs to develop. That’s what is going to let us develop an overall indicator of health, a Dow Jones of Health. But we’re not very close.” Yet.
You can participate in the American Gut Project at americangut.org, or visit the Gut Instinct online forum at gutinstinct-ucsd.org.
