Meanwhile, uBiome emphasized “citizen science,” with contributors formulating the hypotheses to be tested: “How does alcohol consumption change the microbiome?” or “What effect does a vegetarian diet have?” When Will Ludington, a co-founder, became a father in December, he began collecting daily fecal samples from his newborn son, Dylan, to answer his own question: “What is the succession of microbes colonizing the infant gut during the first year of life?”
Microbiome excitement has spread to venture capitalists, who have so far invested in at least four start-ups with the aim of developing new microbiome-focused drugs and diagnostic tools. At Second Genome outside of San Francisco (motto: “The most important genome in your body may not be your own”), chief executive Peter DiLaura has nearly $10 million in seed money and a plan to get to clinical testing within three years for drugs targeted at common conditions like ulcerative colitis, where the microbiome probably plays a causative role.
That timetable may seem optimistic, especially given that research on the first genome—that is, the human genome—has barely begun to produce the abundance of new therapies originally predicted. But at least in theory it ought to be easier to manipulate individual microbes. According to researchers in the field, several major drug companies working on diabetes and obesity now have research units dedicated to the microbiome. The big toothpaste and mouthwash companies are also investigating microbial methods to prevent tooth decay.
Even before such products come to market, merely being able to characterize a person’s microbiome may yield direct medical benefits. Research suggests that each of us has a distinct microbial fingerprint, with individual variation based on diet, family, medical history, ethnic or regional background, and a host of other factors. These differences seem to matter in ways both large and small. For instance, a person may have certain gut bacteria that alter the effect of a drug—even blocking a remedy as common as acetaminophen, the pain-relieving ingredient in Tylenol. At present, doctors sometimes fumble from one prescription to the next before finally hitting on the drug that helps a given patient. The ability to consult that patient’s microbiome profile could make it easier to get there on the first try.
Even so, some researchers worry that the microbiome movement may be promising too much too soon.
When a scientific team recently suggested that changes in gut bacteria could protect against stroke, Jonathan Eisen of the University of California at Davis lambasted them for “absurd, dangerous, self-serving claims that completely confuse the issue of correlation versus causation.” Eisen, a specialist in microbial genomics, now regularly presents “overselling the microbiome” awards on his blog. He says he doesn’t doubt the ultimate importance of the microbiome: “I believe the community of microbes that live in and on us is going to be shown to have major influences.” But believing that “is different from actually showing it, and showing it doesn’t mean that we have any idea what to do to treat it. There is danger here.”
For instance, probiotics, dietary supplements containing live bacteria, are generally harmless. Most contain the same microbes people have been consuming more or less forever. But exaggerated reports about beneficial microbes may lead people to regard the supplements as a cure-all, warns Richard Sharp, a bioethicist at the Cleveland Clinic. Manufacturers are careful not to claim specific health benefits because that would force them to undertake the kind of safety and effectiveness tests required for drugs. “But if somebody says they have a cure for everything,” says Rob Knight, “it’s probably a cure for nothing.” Still, U.S. probiotic sales were up 22 percent last year.
Researchers say they are only beginning to realize how subtle the interactions among our microbial species can be. They hope ultimately to develop probiotics that are correspondingly precise. But in the meantime, if the microbiome is like a symphony, then adding in current probiotics may be the equivalent of performing the piano solo with your elbows.
In certain rare circumstances, hitting the wrong notes may prove deadly. Administering probiotics before treatment seemed to make sense to the physicians in one study of severe acute pancreatitis, a bacterial inflammation of the pancreas. The theory, says the lead author, a Dutch gastroenterologist named Marc Besselink, was that a dose of beneficial microbes might crowd out dangerous microbes. That kind of “competitive exclusion” has worked well in some other conditions. But the pancreatitis patients receiving probiotics died more than twice as often as those who did not. The deaths occurred only in the most severe cases, where organ failure was already underway, and there was nothing to raise concern about the way most people use probiotics. But it was a wake-up call: The microbiome is a complicated system and we are only beginning to understand what happens when we tinker with it.