some of the bioactive small molecules produced by bacteria, but they have just begun to scratch the surface.

According to Julian Davies, a microbiologist and professor emeritus at the University of British Columbia, there are about 1030 bioactive small molecules in the biosphere.
ONE OF THE CHALLENGES researchers face in developing drugs that target biochemical pathways between a human host and its microbiome is what Jonathan Braun, a physician and researcher at the University of California, Los Angeles, School of Medicine calls the hit-and-run effect. Chemicals produced by the microbiome can affect human physiology during unique windows of time, particularly during early childhood, he explains. Even if later on your microbiome totally changes, or you decide to therapeutically modify it, it might not matter because that unique impact it had on our physiology has already taken place. Some researchers are studying a completely different way of manipulating the human microbiometransplanting feces from a healthy donor into a patient suffering from a particular disease. The donor material is typically introduced into the patient by colonoscopy or as a suppository. Physicians have had some success in performing fecal transplants in patients with recurrent Clostridium difficile infections. Such infections cause severe, chronic diarrhea that can be life threatening. For example, Elaine O. Petrof, a professor of microbiology and immunology at Queens University School of Medicine, and colleagues published whats being called the repoopulate study earlier this year (Microbiome 2013, DOI: 10.1186/2049-2618-1-3). They showed that a stool substitute made from 33 different intestinal bacteria isolated in pure culture from a single healthy donor could be used to treat recurrent C. difficile infections that had failed to respond to repeated treatment with antibiotics. Although fecal transplants appear promising for treating C. difficile, physicians are performing the procedures without any particular protocols, warns Alexander Khoruts, a gastroenterologist and immunologist at the University of Minnesota. And, he notes, some patients are doing the procedure on themselves for a variety of indications, among them irritable bowel syndrome, arthritis, and autism. A concern on the horizon is that as the microbiome gives up its secrets, researchers will turn to synthetic biology as a means

to manipulate it. Any products developed via this route could still be classified by FDA as food or dietary supplements, in which case they would not be subject to regulatory review of safety and efficacy. Synthetic biology could expand the life span of bacteria and viruses, says Rosamond Rhodes, a professor of medical education and director of bioethics education at Mount Sinai School

of Medicine. Synthetic biology could also be used to make bacteria in probiotics more resistant to mutation. Synthetic biology could be useful, but it could also be dangerous, Rhodes cautions. Scientists are just beginning to understand the human microbiome, she says. A great deal will have to be learned before the microbiome interventions become feasible.

CEN . ACS.ORG

23

AUGUST 1 2 , 2013