September 2014 Issue

Mapping the Gut Microbiome — An Ambitious Project That Could Lead to Better Gastrointestinal Health
By David Yeager
Today’s Dietitian
Vol. 16 No. 9 P. 12

Many people are familiar with the Human Genome Project, which identified all the genes in human DNA and determined the sequence of the 3 billion chemical base pairs that comprise it. However, another project is under way that’s no less important and arguably more ambitious under the auspices of the National Institutes of Health: the Human Microbiome Project. And many of the largest labs in the country are participating.

The first phase of the project was conducted from 2007 to 2012 and focused on developing data sets and computational tools to describe the composition and diversity of the microbial communities that live in and on our bodies. The second phase, which began in 2013 and runs until 2015, aims to create the first integrated data sets describing the biological properties of interactions between microbes and humans.

The research still is in an early phase, but the insight it will give scientists likely will affect how we maintain health and treat disease, especially digestive disease. Justin L. Sonnenburg, PhD, an assistant professor of microbiology and immunology at Stanford University School of Medicine in California, didn’t participate in the initial phase of the Human Microbiome Project, but his lab studies how intestinal microbes affect our biology. He says one thing that’s becoming clear is that microbes play a crucial role in our lives.

“All of this [research] collectively has created a huge paradigm shift for biomedicine in general and brought to light the realization that we’re not just collections of human cells. The individual is much more than that,” Sonnenburg says. “We’re actually composite organisms. We’ve coevolved with these microbial communities, which are integrated into virtually all facets of our biology in some direct or indirect way, and so we have to somehow incorporate these bacteria and other microbes into our conceptualization of health and determine how we should conduct medicine [going forward].”

Sonnenburg, who prefers the term “microbiota” to describe the communities of microbes in our bodies and refers to the microbiome as the collective genome of those microbes, says no two microbiota are the same. He notes, however, that while there are noticeable differences between healthy and unhealthy individuals, it’s too early to draw conclusions about what constitutes an optimal microbiotic community. For example, obese people as a population tend to have different microbiota than average, healthy individuals, but some obese individuals also don’t have dysbiotic (unhealthy) microbiota. Likewise, some lean individuals have microbiota that are similar to those who are obese.

Sonnenburg says mouse studies have shown that microbiota associated with obesity can make lean mice obese, demonstrating that such microbiota can transfer to lean individuals. A previous human trial demonstrated a short-lived but measureable decrease in factors associated with the metabolic syndrome, such as insulin resistance and glucose tolerance, when microbiota were transferred from a lean individual to someone who was obese, he says. Unfortunately, the processes that cause these reactions aren’t well defined. What’s needed is increased study on the basic mechanisms that connect microbial and human biology, he explains.

Tuning an Organ?
Defining those mechanisms will take some time; the microbiome is 100 times larger than the human genome. It’s been estimated that there are 10 times as many microbial cells in and on our bodies as there are human cells, but human cells have significantly greater mass. Although microbes add only a few pounds per person to overall weight, they perform a variety of functions on which our bodies rely.

“The microbiome makes up 1% to 2% of the adult body, so it could essentially be considered a separate organ,” says Kristi L. King, MPH, RDN, CNSC, LD, a senior pediatric dietitian at Texas Children’s Hospital, clinical instructor at Baylor College of Medicine in Houston, and spokesperson for the Academy of Nutrition and Dietetics. “Previously, we thought it was just there to help us with the digestion of foods and the production of certain vitamins, such as vitamin K or vitamin D, but now we’re seeing that it’s playing a much bigger role than that. The data isn’t really there yet for us to definitively classify it, but that’s the current hypothesis. We’ve just scratched the surface of knowledge about this 1% to 2% of the human body that, for so long, we haven’t known anything about, and I’m really excited to see where this research goes.”

King says certain microbes are important for intestinal health. For example, probiotics have been shown to help with certain infections, such as Clostridium difficile, and fecal transplants have been shown to relieve symptoms of C difficile and ulcerative colitis. Baylor University researchers, who participated in the Human Microbiome Project, also have studied how microbes affect drug metabolism, which can help to measure the effectiveness of certain drug therapies.

King says each person’s microbiota is like a fingerprint, and determining how those thousands of microbes affect food metabolism will open all sorts of possibilities. With all of the talk of personalized medicine in areas such as data analysis and medical imaging, research on the human microbiome may lead to the most personalized treatments of all: diets tailored to specific individuals based on their personal microbial communities. Already, there’s some movement in this direction with diets designed to treat certain medical conditions.

“We know that people with IBS [irritable bowel syndrome] have certain intolerances, and that’s where FODMAPs have become really popular,” King says. “Is it really that the patients are unable to digest those particular carbohydrates or is their microbiome contributing to that? That, I think, is probably our first inclination of how [personalized diets are] going to go.”

Sonnenburg says that as these mechanisms are better understood, it likely will be possible to add beneficial microbes, such as specific probiotics that are highly effective at competing with harmful microbes, to individual microbial communities. He adds that it even may be possible to add either engineered or nonengineered strains of microbes to improve immune function. He cites the higher incidence of allergies and asthma in Western civilization, compared with societies that eat a more “primitive” diet, as a clue that modern life may have fundamentally changed our relationship with our guts.

“There’s a developing theory that the microbiota of healthy Westerners actually may be an unhealthy microbiota that’s predisposing us to a lot of Western diseases, and the idea is that we actually evolved with a microbial community in our gut that looks very different from the microbiota we have now,” he says. “Our immune systems are no longer recognizing an entity that they’re used to interacting with. This may be predisposing us to a proinflammatory state that’s the basis of all these Western diseases. We may now have somewhat of a foreign entity residing inside our gut that no longer is recognized and interacting symbiotically with our human genome because our human genome evolved with a different microbial community.”

Sonnenburg says modern practices such as cesarean sections, antibiotic use, and low-fiber diets as well as overly sanitized environments and food supplies have led to a major decrease in the diversity and function of human microbiota and may be predisposing us to conditions ranging from allergies and asthma to Crohn’s disease and cancer. Although microbiota can quickly change in ways that aren’t always predictable, there are some steps people can take to maintain their microbial health.

Sonnenburg has studied how microbiota react to changes in diet and says certain parameters are taking shape. One recommendation is to eat a high-fiber diet. Many people essentially are starving certain species of beneficial fiber-eating microbes in their intestines, he says, adding that overuse of antibiotics is a problem, too, in that they can decimate microbiotic communities, and it’s unclear whether those communities ever recover. He adds that breast-feeding also is important because it helps to properly colonize infant digestive tracts, which basically are sterile at birth.

In terms of diet, Sonnenburg says fermented foods and probiotics may be important for regulating gut responses in microbial communities. He recommends foods such as kefir, yogurt, and kimchee and expects designer probiotics to play a larger role in treating disease and maintaining health. Ultimately, understanding what an optimal microbiota is for any given individual will allow clinicians to implement highly targeted treatments. They just need to be aware of unintended complications.

“We need to think about how to take all of the technological and medical advances of the modern world and make sure that those are not used in ways that lead to detrimental health effects because of collateral damage to the microbiota,” Sonnenburg says.

— David Yeager is a freelance writer and editor based in Royersford, Pennsylvania.