After a trip to Peru last year, microbiologist Rob Knight came home with a horrendous case of traveler’s diarrhea. He took some antibiotics and quickly recovered. But because Knight had been participating in one of his own studies of the human microbiome–the diverse collection of bacteria and other organisms that inhabit our gut, skin, mouths, and other parts–he could examine how the drugs changed the microbial population in his gut. Microbes did repopulate his digestive tract, but the community makeup was different.
Soon after his trip, Knight restarted a diet and exercise program that had previously proved ineffective at helping him lose weight. This time around, he lost 60 pounds. His mind went straight to his microbes. Previous research from his lab at the University of Colorado, in Boulder, showed that microbes can have a transmissible effect on weight–transplanting microbes from fat, hungry mice into normal mice causes the recipients to eat more and gain weight. “The conjecture was that the antibiotics might clear out the microbes that were already there and make it easier to reshape the community,” says Knight.
Of course, not everyone who takes antibiotics loses weight. And livestock are routinely given the drugs to beef up rather than slim down. But a growing body of evidence suggests that our microbes vary greatly from person to person and play a key role in both metabolism and obesity. By cataloging the variability in different individual’s microbial communities, as well as how those communities change in response to certain drugs or other environmental factors, scientists hope to harness the malleability of our microbes for medical uses.
The microbes that inhabit our bodies–we each have 10 times as many microbial cells as human ones–are a vital part of our health, breaking down otherwise indigestible foods, making essential vitamins, and even shaping our immune system. Recent research links changes in these microbes to diseases, such as ulcers, heart disease, and obesity. Because the vast majority of these organisms cannot grow outside their host environment, they have been difficult to study. But faster, cheaper sequencing technologies have given scientists a new way to examine the contents of entire microbial communities both in our guts and in the broader environment.
“Humans are superorganisms with two genomes, the genetically inherited human genome (25,000 genes) and the environmentally acquired human microbiome (over 1 million genes),” writes Liping Zhao in a recent review published in the Journal of Biotechnology. “In contrast to the human genome, the gene composition of the human microbiome is rather flexible and can be modulated by foods and drugs.”
Much of the early research using sequencing to study microbes has focused on cataloging the variability between the communities inhabiting different parts of the body, different people, and people with different diseases. But scientists are now starting to examine how specific interventions, such as diet or drugs, alter these communities. They hope to translate the findings into diagnostic tests that can help to predict which patients will experience side effects from antibiotics, or the best diet option for a certain individual. “There are lots of thing we can do potentially right now using microbes as markers,” says Knight.
In research presented at a recent conference in China, Zhao and collaborators analyzed people’s microbial communities before putting them on a specialized diet. Some gained weight and some lost it. Zhao was able to predict who would benefit by looking at the makeup of that person’s microbiome prior to the diet.
Knight points out that China is an ideal location for this type of research for two reasons: BGI, a sequencing center in Beijing, has massive sequencing power (the institute is expected to surpass the entire sequencing capability of the United States later this year). “And you have access to a large population of people willing to engage in research like being restrained in what they eat for a long time,” he says.
Knight is collaborating with Jeff Gordon at Washington University, in St. Louis, to analyze how gut microbes affect children’s ability to put on weight. Food supplements of peanut butter, milk powder, and vitamins have helped many children suffering from malnutrition in poor countries. But a substantial number don’t respond; in some cases, identical twins living in the same house and eating the same food will respond differently. “Have they picked up some pathogen causing malnutrition or lost some kind of microbe?” says Knight, who ultimately hopes to develop a cheap diagnostic test that would enable tailored supplements.
The two scientists are also studying Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease, which flair up periodically in sufferers. “We want to understand how the microbial community changes between relapse and then potentially use that for treatment,” says Knight.
Preliminary research in David Relman’s lab at Stanford highlights what antibiotics do to our gut microbes. His team analyzed the microbiomes of healthy people given two five-day courses of the antibiotic Cipro six months apart. Individuals responded very differently to the drugs. “We see a drop in abundance related to Cipro and a drop in diversity,” said Relman at a talk at MIT last week. “Some people go back to predrug diversity and some don’t.” After the second exposure, the microbial community never returns to the initial state. “Maybe someday we will be able to predict who will be susceptible to antibiotic-linked problems, like diarrhea or colitis,” he says.
Relman’s study highlights the potential complexity of studying antibiotics and weight loss. Despite his own experience, Knight certainly doesn’t recommend taking a course of antibiotics to lose weight: “That’s like weeding a garden with a bulldozer and hoping what grows back is what you want,” he says. “We want a much more specific way to control these communities.”
Knight offers another potential explanation for his weight loss–that he is recording both his food intake and exercise routine as part of the experiment. “When you know people in the lab will be going over your records, you might be more conscious of what you’re doing,” he says.