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reset her microbial ecosystem and likely raised more than a few eyebrows. Physicians performed a fecal microbiota transplant (FMT), in which diluted stool from a donor is transplanted into the suffering patient via colonoscopy, depositing the donor stool and the healthy microbiota contained therein as far into the colon as possible to allow it to repopulate the recipient's gut flora. "It's like taking an old trash dump and reseeding it with plants to grow into a forest," Knight analogizes. "You're promoting the growth of a community that's going to be stable and restored to a high level of ecosystem functioning." A f ter just one FMT treatment, Hunter's CDI was resolved, in keeping with the procedure's reported 90 percent success rate. When combined with an additional round of the antibiotic vancomycin, the success rate jumps to 98 percent. Seeking causality Researchers' explorations into the efficacy of bacterial therapies — the overarching treatment category to which FMT belongs — for other disease processes currently focuses on demonstrating causal relationships between gut microbiota and disease, Knight says. "One of the problems is establishing causality," he says. "Do microbes cause disease, or does the disease cause an alteration in the host that is also reflected in the change of microbes?" For example, ongoing studies seek to explore and identify causal relationships between gut microbes and obesity. At Washington University, Jeff Gordon (with whom Knight frequently collaborates) uses germ-free mice with no microbes of their own to examine how microbes affect nutrient utilization. After separating the microbe-less mice into groups, Gordon introduces them to microbes from obese or lean mice and then observes their weight following microbe introduction. "If you take the microbial community from obese or lean mice and transplant it into germ-free mice, what you see is their ability to use nutrients depends a whole lot on which mouse's microbial community they got, and that's how we establish causality," Knight explains. While gut microbiota may prove a boon in the fight against obesity, Knight relates that studies examining the relationship between gut microbiota and diabetes, non-alcoholic fatty liver disease, multiple sclerosis, colon cancer and even neurodegeneration are under way. Although results are a few years off, they may provide valuable new treatment avenues for a variety of disease and behavioral processes. changing the landscape Knight explains that breakthroughs in microbiome research are recontextualizing how seemingly unrelated disorders are seen and are reframing the way physicians think about even apparently unrelated conditions. "A more interesting question may be, 'In what conditions can we rule out any microbial involvement? You might think something like Down syndrome may be a good example of a genetic disorder where microbes cannot be involved, but there have been some reports that oral microbiota is substantially different between cases and controls," Knight explains. "So microbes seem to be having all kinds of effects we never suspected on our disease susceptibility, physiology and even our behavior." ■ a complicated tasK While the possibilities for microbiota and bacterial therapy's utility continue to multiply as researchers discover more and more about the human microbiota, the u.s. food and drug administration currently requires an investigational new drug application to employ fecal microbiota (fMt) transplant for conditions other than Clostridium difficile infection. "if you want to use it for some of these other disorders, the regulatory burden is very high," says rob Knight, Phd, associate Professor at the Biofrontiers institute of the university of Colorado Boulder, "whereas if you want to use it for patient stratification, the pathways to do that diagnostic test are potentially much shorter." Knight explains that, instead of testing human genes tied to drug metabolism, researchers can test for bacterial genes associated with the same metabolism to find the patient population most responsive to that drug. if patients are found to have contraindicating bacteria, fMt could be used to reset the gut microbiota, making the patient amenable to medication. "if you found you couldn't take a drug because you have some bacterial species that would break down or recycle it into the bloodstream after it was deactivated by the liver to a dangerous level, the prospects of getting rid of those bacteria are really exciting," Knight notes. mdnewS.com ■ MD News Greater Boston | 17

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