The newest results from the Human Microbiome Project have revealed just how connected the microbes in our gut are to our overall health.
You have about as many bacteria and other microbes living in your body as your own cells—and yet, we still don’t understand much about how this microbiome relates to bodily function. Back in 2007, the National Institutes of Health kicked off the Human Microbiome Project, a $200 million effort to understand these microbes. Scientists have now published the results from the second phase of this project, designed to study how the microbiome interacts with the human body. These three studies, which examine preterm birth, inflammatory bowel disease, and pre-diabetes, demonstrate that microbiomes are unique to individuals and intimately tied to our health.
“The big take-home across all of these studies is that we’re starting to realize in medicine, we can’t just use common parameters for all people... our health is more personalized,” Lita Proctor, former Human Microbiome Project coordinator at the National Human Genome Research Institute of the National Institutes of Health, told Gizmodo. “And unless we include the microbiome in routine health assessments of people, we’re missing a big piece of the story.”
The first phase of the project analyzes the microbes in the body in order to figure out what species inhabit us. It’s not obvious what purpose these microbes serve—E. coli, for example, is plentiful inside our gut, but if it enters our body from the outside, it can be deadly, Proctor explained. So the second phase of the project looked at the interplay between these microbes and our bodies. The second phase included three studies, each monitoring a different aspect of the human microbiome and its relationship to our health.
One study, published in Nature Medicine and led by scientists at Virginia Commonwealth University, focused on the relationship between the vaginal microbiome and preterm birth. Around 15 million preterm births occur annually around the world, and it’s a common cause of infant mortality. But past studies have shown that while genetic factors play a role, so do environmental factors, such as the microbiome, particularly among women of African ancestry, according to the study. Scientists took approximately 12,000 vaginal microbiome samples from 1,572 pregnancies. The researchers also conducted a more in-depth study of 45 people of African ancestry who experienced preterm birth, alongside 90 who didn’t for comparison.
They found that those who delivered early babies had significantly lower vaginal levels of Lactobacillus crispatus and higher levels of several other bacteria. They also found higher levels of cytokines, chemicals associated with immune system activity. The research could potentially offer a new kind of screening to determine whether someone is at risk for a preterm birth.
Two other studies instead focused on the gut microbiome. One, led by scientists at Stanford University and the Jackson Laboratory in Connecticut, followed 106 people, both healthy and with pre-diabetes, for four years, profiling things like the metabolic chemicals in their cells, the chemicals produced by their immune systems, and the proteins in their cells, as well as changes in their gut and nasal microbiomes.
They found noticeable changes to the both healthy and pre-diabetic participants’ microbiomes during viral infections, potentially protective changes after they got vaccines, and differences in the way that healthy and prediabetic patients’ microbiomes responded to viral infections. They also found differences in the way microbes interacted with the rest of the body between healthy and pre-diabetic individuals.
Perhaps most surprisingly, the researchers were able to see changes in the study participants’ immune system before the onset of type-2 diabetes. The researchers hope that their results can serve as a resource to further study healthy, pre-diabetic, and type 2-diabetic people.
“We’re learning how this whole symphony plays out,” study lead author Michael Snyder from Stanford University told Gizmodo. “These things are highly interrelated and we’re beginning to understand what that relationship is.”
A final study, led by scientists at the Broad Institute of MIT and Harvard University, focused on perhaps the most well-known microbiome-linked disorders, inflammatory bowel diseases like Crohn’s disease and ulcerative colitis, which affect millions around the world. Researchers followed 132 subjects for a year, collecting stool and blood samples and analyzing their cells. They found telltale changes to the body and microbiome during disease flare-ups, and pinpointed a clade of microbes that seemed to go missing in patients with IBD.
It’s not clear if the microbiome changes set off the other changes, or if the microbiome changes are the consequence of other changes in the body. But scientists are getting closer to establishing what causes what, study author Curtis Huttenhower, professor of computational biology and bioinformatics at Harvard, told Gizmodo.
“What we know from the time course is that, within individual subjects, there are coordinated changes in the microbiome and immune system that activate during flares and resolve after flares,” he said. “We can’t know whether they’re causal or not, but we know what we can test outside of people in order to see whether these microbes or chemicals” are causing the flares.
Reading about all of these studies, you might wonder what you could be doing to bolster your own health. We’ve written in the past that American diets seem to result in a decrease in microbial diversity in mice, for example. The researchers all advised against taking antibiotics unless absolutely necessary. They also warned against taking probiotics, which aren’t regulated and have unclear impacts on our microbiomes. But each of the researchers recommended a diverse diet high in fiber.
It’s still unclear what it means to have a healthy microbiome or what an unhealthy microbiome looks like, Proctor wrote in a Nature perspective, and that’s an important next avenue of research. But thanks to the efforts, as well as over a billion dollars in research funding toward the topic, we now know just how important the microbiome is to maintaining our health, and that changes in our microbes are intimately connected to changes in our health.
There’s a lot more work to do. Researchers hope to make observations of the day-to-day variability of the human microbiome, wrote Verónica Lloréns-Rico and Jeroen Raes from KU Leuven in Belgium in a Nature commentary. They’d also like to see more quantitative work analyzing the how the bacteria identified in the studies compare to the total population of bacteria in our bodies, along with replication of the work across diverse populations of people.
But the second phase of the Human Microbiome Project is important for reasons beyond just these results. It offers a lot of data that researchers can use to further elucidate the connections between these microbes and our bodies, and that could help biotechnology companies come up with innovative treatments.
Our bodies are more than just human cells. They’re a complex agglomeration consisting of ourselves and the hundred trillion microbes that live inside of us. And research is making it strikingly clear that these microbes wield a formidable level of control over our lives.