The scoop on poop: Microbiome Project finding critical roles for bacteria in good health

By Diane Carman

The next time you pressure your doctor to prescribe antibiotics to treat a cold, think about this: while they’ll do nothing for the cold, the bacteria-killing drugs could affect your weight, your vulnerability to bowel disease or hardening of the arteries, even your sex life.

One of many bacteria in the gut.

One of many strains of bacteria in the gut.

Scientists working on the Human Microbiome Project are just beginning to understand the powerful role bacteria play in our health and well-being, and a team of Colorado scientists are on the cutting edge of that research.

“Microbe-based therapies can actually cure people,” said Rob Knight, a professor in the Department of Chemistry and Biochemistry, and the BioFrontiers Institute at the University of Colorado Boulder. But these therapies are not available in doctors’ offices yet. “It’s important to do the additional research,” he said.

Knight joined Catherine Lozupone, assistant professor at the CU School of Medicine, and Nadim J. Ajami, a research associate at the Baylor College of Medicine, for a panel discussion on microbiome research at the Association of Health Care Journalists conference in Denver last month.

Some of the most promising research is focused on the use of fecal transplants to treat patients with Clostridium difficile, commonly known as C. diff, a life-threatening bacterial infection in the gut usually related to antibiotic use.

“The big splash in the microbiome world” is the potential for treating C. diff, said Ajami, who quipped that the treatment involves “repoopulating” the gut with the beneficial bacteria wiped out by antibiotics.

While the research has been encouraging, clinical trials are still under way, she said, and medical protocols are yet to be developed.

Human Microbiome Project

Human Microbiome Project

Fecal transplants have shown “tremendous promise” in treating C. diff, Knight said, so much promise that sufferers have engaged in their own dangerous experiments and even have posted a do-it-yourself fecal transplant video on YouTube.

“I strongly caution against this,” he said.

Rob Knight

Rob Knight

Knight said that the FDA is still trying to determine how to regulate fecal material, both for use in research and ultimately for use in treatment. Stool currently is regulated as “human tissue,” which restricts its availability for research purposes and would seriously limit its therapeutic use. To enable physicians eventually to transplant fecal material to restore the flora in the gut, FDA rules would have to be changed to recognize stool as a drug.

Similarly, the frenzied marketing of probiotics to treat a whole range of digestive ailments is premature – at best – and not evidence-based, the scientists said.

“People think probiotics are interchangeable,” said Knight. “That’s not a very good assumption. The complexity (of microbes) is much greater than that of drugs,” so determining which beneficial bacteria are missing in the gut and how to replace them is much more complicated that buying a random bottle of probiotic supplements at the grocery store.

“The public’s enthusiasm is substantially in advance of where we are,” Knight said.

What they do know

While the scientists caution against rushing unproven therapies into practice, in the last decade they have made tremendous strides in understanding the human microbiome.

Thanks to the success of the Human Genome Project in developing techniques for mapping the DNA of all of the cells in the human body, “it’s a million times cheaper to root out the DNA in microbes than it used to be,” Knight explained.

Excitement over the microbiome research also has sparked a burst of interest in the field of microbiology after decades of declining enrollment in those courses of study and a dwindling pool of potential microbiology researchers.

Knight said that the discovery of antibiotics in the 20th century led scientists to believe that there was little left to explore in microbiology. The $173 million-dollar Human Microbiome Project has changed all that.

The scope of the project is extraordinary. Scientists working on the Human Genome Project had to map a mere 10 trillion human cells while 100 trillion microbes that populate the body must be sequenced to understand their roles in our whole array of bodily functions.

“Under a microscope, they all look the same,” Knight said.

In addition to sequencing the DNA, the scientists have had to create software tools to enable them to visualize the data and turn them into useful information.

One hundred trillion microbes translates to about three pounds per person, Knight explained. The major sites on the body for these colonies are the mouth, the gut, the skin and the vagina, and the scientists have found that the populations of those colonies change dramatically over time.

It takes infants two to three years to develop the range of gut bacteria in the average adult. For both adults and children, a round of antibiotics creates a temporary setback in the diversity of that microbial colony.

“We also know that antibiotics in the first six months of life are linked to obesity later,” Knight said.

Based on gut microbes, Knight said, doctors can predict whether a child will be lean or obese with a 90 percent accuracy rate. The accuracy rate for predicting obesity using genetic information is only 60 percent.

The scientists have found that adults with Crohn’s Disease have “more infant-like” microbe colonies in their gut. Similarly, patients on chemotherapy or those with C. diff also have infant-like gut bacteria.

“It’s like developing a forest over time,” Lozupone said, and drug treatment or illness can clear cut large portions of it.

Catherine Lozupone

Catherine Lozupone

A healthy infant has lots of E. coli bacteria in the gut, but that’s not healthy for adults. Even across healthy adults, the range of microbes in the gut is striking, she said, and those differences are strongly related to diet.

“The microbiome adapts to diet,” she said. “I do think we can eat in such a way to promote a healthy microbiome.”

She recommended “complex foods that leave something behind to fuel the microbes.” A high-fiber diet of vegetables, fruits and whole grains is “healthy for everyone,” she said. A diet high in refined sugar, which is digested quickly and metabolizes right away, is not as likely to fuel a healthy microbial colony in the gut.

C-sections and obesity

Among the theories the scientists are exploring is the relationship between increased C-section rates and higher rates of asthma, autoimmune conditions and obesity later in life.

Knight said when a C-section delivery was required for his child, he transferred microbes from his wife to the newborn in an attempt to mimic the beneficial effects of vaginal delivery.

“No one knows if obesity is affected by the transfer of vaginal bacteria during childbirth,” Knight said, but scientists are exploring that hypothesis as well as other beneficial effects of vaginal microbes.

It’s an example of how much progress has been made in understanding the role of the microbiome in health – and how much remains to be discovered.

The scientists know that microbes on the skin influence whether mosquitoes will bite one person and not another. They know that bacteria help determine sexual attraction between people, that oral bacteria play a part in developing hypertension, and that microbes play some role in development of obesity, diabetes and countless other conditions.

But there’s still a vast frontier of knowledge left to explore.

Some of it is taking them back in time.

Scientists are harvesting fecal material from mummies, from the bodies of climbers left on the slopes of Mount Everest, even from the bodies of Vikings trapped in permafrost.

“We’re looking at the pre-antibiotic era of the microbiome,” Knight said.

Understanding that will offer one more clue to the role that a universe of bacteria plays in human health.

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