Injecting molecules from a sea slug that received tail shocks into one that didn’t made the recipient animal behave more cautiously.
Seres Therapeutics’s microbiome-targeting therapy for recurrent Clostridium difficile infection fails a Phase 2 clinical trial.
August 1, 2016|
WIKIMEDIA, CDC, HOLDEMANEarlier this year, Seres Therapeutics published promising data from an early-stage trial for its SER-109, a pill containing bacterial spores isolated from stool samples for patients with recurring Clostridium difficile infections (CDIs). The therapy seemed to be effective. But results announced last week (July 29) from a Phase 2 trial of 89 people with recurrent CDI were less positive: researchers found no significant difference between the treatment and control groups.
“The results were surprising, especially since the [Phase] 1b data was eye-popping,” Roger Pomerantz, the company’s CEO and president, told The Atlantic. “We’re now trying to dissect why there was a difference in the two trials.”
While the results may be a setback for SER-109, microbiome-based drugs still look promising, Diane Hoffman, director of the Law and Health Care Program at the University of Maryland and chair of a working group studying microbial transplants, told BuzzFeed News. “I still think it’s really exciting—maybe we just ruled one thing out,” she said. “I have this theory that there’s something potentially unique about the composition of microorganisms together that produces the beneficial effect. When you deconstruct that, you lose some of that benefit.”
Another company, Minnesota-based Rebiotix, is also developing a drug for antibiotic-resistant CDI. Whereas Seres researchers select specific bacterial species they put in the company’s treatment, Rebiotix’s drug, which completed enrollment in a Phase 2B trial last November, uses a suspension of all bacteria found in a donor stool sample.
August 2, 2016
What Diane Hoffman said is insightfully correct and should be engraved into researchers' minds:
“I have this theory that there’s something potentially unique about the composition of microorganisms together that produces the beneficial effect. When you deconstruct that, you lose some of that benefit.”
Fecal transplantation (FT) is not the same as merely sprinkling pre-packaged seeds in a prepared garden bed, green-thumb Seres. The point of FT is to meld two microbiomic ecosystems. Throwing spendy seeds into an established, though undesired, eco-landscape is like squirting Moët champagne to stop the tide.
What must be done is to innoculate subjects with a representative subset of the desired microbiome, perhaps by stages. Trust that the established system is not going to be receptive. Moreover, all ecosystems, despite being located in the same 'climate', are different. Therefore, a first goal might be to gain a 'beachhead' in each (different) profiled subject system and augment it as in ecological succession.
However, like gardening individual plots, you'll have to get your hands dirty; it won't be easy.
August 4, 2016
I have absolutely no hard information about this sort of thing, but ever since I first heard of faecal transplants, I have suspected that the operative factor might be bacteriophages and some of their phage-tolerant host bacteria, rather than simply competitive bacterial cultures. That certainly could be logically compatible with unpredictable outcomes of transplants, especially of notionally pure cultures.
Bacterial competition definitely could be significant as well of course; in fact it is altogether plausible that some strains of bacteria could harbour phages as offensive competitive weapons against strains that were not adapted to survive phage infection, in which case the failure documented here might simply be because of too-obsessive purification of the spores leaving them phageless.
It is a messy environment aft of the caecum of course, and accordingly not very predictable. There have been some very curious side effects following on transplants.
I also suspect that the human appendix is not a totally functionless and troublesome vestige, quite apart from its immune functions; I bet that an unoccluded appendix is a refuge for gut flora during periods of severe diarrhoea and the like, from which the colon can be recolonised. I wonder whether faecal transplants might be particularly effective if they were particulalry directed to colonise (if you will excuse the term) the appendix.