Perhaps the most well-known disease-causing gut organism is the bacterium Helicobacter pylori, which can trigger peptic ulcer. In the past few years, scientists have linked obesity to the relative abundance of two dominant intestinal bacterial phyla and found that dysfunctional intestinal bacteria are associated with nonalcoholic fatty liver disease, inflammatory bowel disease and some types of cancer. Nicholson even speculates that the organisms could play a role in neurological disorders, such as attention-deficit hyperactivity disorder, Tourette’s syndrome and autism. “We have some evidence now that shows that if you mess around with the gut microbes, you mess around with brain chemistry in major ways,” Nicholson remarks. He currently collaborates with microbiologists to match metabolites with specific bacteria—there are thought to be 1,000 species and more than 10 trillion bacterial cells inside us at any given time.
This identification process has only recently become possible. Although scientists have been able to extract gut bacteria from fecal samples for many years, it has been next to impossible to culture the samples afterward because they survive only in highly acidic, oxygen-free environments. Thanks to new DNA-sequencing technologies, scientists can now identify gut bacteria fairly easily, and there is growing interest in doing so: the National Institutes of Health launched its Human Microbiome Project last December with the goal of fully characterizing the human gut flora.
Once investigators can correlate metabolites with health, it may one day be possible, Nicholson says, to make urine sticks similar to those used in pregnancy tests to regularly check the fitness of our gut flora. Some companies have already begun selling food products to help keep these populations in line—with live beneficial bacteria (probiotics) or compounds that help these species grow (prebiotics), or combinations of the two (synbiotics). Unfortunately, these medications typically fall into the category of “functional foods,” which means they are rarely tested in clinical trials. One exception is VSL #3, a combination of eight bacterial species sold in packet form by the Gaithersburg, Md.–based VSL Pharmaceuticals. In double-blind, placebo-controlled trials, the colonies effectively treated ulcerative colitis and irritable bowel syndrome.
Many possibilities exist for bug-based drugs, and there is a strong need for them, Nicholson maintains. According to a study published by scientists at the pharmaceutical giant Pfizer, the human genome offers only about 3,000 potential drug targets, because just a subset of genes produces proteins that can be bound and modified by druglike molecules. But “there are 100 times as many genes in the microbial pool,” says Nicholson, who regularly works with drug companies to better elucidate how people metabolize medicines. He is “one of a few academics I’ve met who’s interested in the pharmaceutical industry for its problems rather than just for its cash,” comments Ian Wilson, a scientist working in England for the pharmaceutical company AstraZeneca. Wilson adds that Nicholson is always full of potential solutions, referring to him as “a bubbling mass of ideas.”
Because genes provide only limited information about a person’s risk for disease, Nicholson dreams of a time when physicians can provide personalized health care on the metabolome. Simple blood or urine tests would detect the risk of cancer or heart disease early enough to begin preventive therapy; drugs would be tailored to each person’s metabolic profile—and in many cases, they would not target our organs but our bacteria. “It opens up visions of a future that we would never have suspected even a few years ago,” Nicholson says. “Many microbiologists might argue this is fanciful, but you only make huge progress in science by thinking almost the unthinkable.”