Editing the microbiome

Abstract

After years of monitoring the body’s microbial communities, researchers are now starting to modify them to treat disease. Put the gut microbes from an obese mouse into the body of a lean one, and the latter will pack on weight—even without changes to its diet, activity, or other habits (1). Such studies have made it increasingly clear that an organism’s commensal microbes can have powerful health effects, including in humans. A decade of research suggests that our microbiota help drive brain development, spur immune-system development or allergies (2), and might trigger certain cancers. These observations have spawned industries that offer probiotics, prebiotics, personal microbiota sequencing, and more. Infections of Clostridium difficile (pictured in scanning electron micrograph) are a particularly attractive target for microbiome researchers, who generally have a good understanding of the pathogen’s interaction with commensal microbes and the gut environment. Image credit: Science Source/Paul Gunning. But few therapeutics actually alter—much less improve—our commensal microflora, in part because watching these microbial dynamics play out is still a step short of understanding their mechanisms well enough to intervene effectively and safely. Already, fecal microbial transplants (FMTs) have demonstrated both the promise and peril of manipulating microbiota. For desperate patients fighting persistent intestinal Clostridium difficile infections, the transplants, in which the entirety of bacteria from a healthy person’s intestines are transferred to those of an ill individual, can offer relief (3). Yet even when FMT works, there’s no way to standardize or quantify its effects. Recent cases of severe side effects—including one death—led the US Food and Drug Administration to halt all clinical trials of FMT until added safety measures are put in place (4). “We really don’t know the long-term consequences of an FMT,” says microbiologist Casey Theriot of North Carolina State University in Raleigh. “It saves lives, but we …