Keeping Bacterial Cures Alive in the Gut

Imagine a medicine that regenerated inside the body, treating a disease or disorder for as long as the patient lived. Such is the promise of live bacterial therapeutics; an inoculation with a microbe engineered to change its host’s biology could cure chronic illness.

Already, some people undergo fecal transplants to cure chronic gut infections with Clostridium difficile, better known as C. diff. Others swear that the transfer of gut bacteria from a healthy donor has helped conditions such as the inflammatory bowel disorder Crohn’s disease, though scientific studies on the procedure for such disorders show mixed results.

One major problem? Though feces are 50% to 80% bacteria, getting a new microbe — especially a bioengineered one — to colonize the gut is actually a huge challenge. Fecal transplants usually have to be repeated, or the host’s gut microbiome reverts back to its status quo. “It’s hard to ask a microbial organism that has never lived in a mammalian gut environment to go to this highly hostile environment and survive,” says Amir Zarrinpar, an assistant professor of gastroenterology at the Univ. of California, San Diego. “They will have to find a niche by competing with thousands of other species of bacteria who have specifically adapted to that particular host. On top of that, they also have to express an engineered transgene that is potentially detrimental to their fitness.”...