A new report from the Memorial Sloan Kettering Cancer Center in New York shows that a distinct population of microbes reintroduced into a patient could clear out rampant Clostridium difficile infections.
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Clostridium difficile is responsible for up to 14,000 deaths per year, and the rates of infection have tripled since 1991. The primary cause of this spread are poor practices by hospitals in quarantining infected patients, and overuse of antibiotics, leading to resistant organisms. Because of this emerging resistance, researchers have been working to find another means by which to alleviate patients of the infection.
Previous efforts have identified a causal link between a healthy gut microbiome and a decreased risk, or elimination of, a C. difficile infection. These teams were able to show that fecal transplant therapy, where a healthy individual donates stool to be ingested by or deposited in the patient, significantly reduced bacterial density in the patient’s gut and led to a 90% cure rate. The hypothesis was that these fecal transplants repopulated the patient’s gut with a healthy microflora, but no one knew what bacteria were truly effective, leading to delay of regulatory approval over safety issues.
Now, the researchers at MSKCC have shown that of the thousands of bacterial species in the human gut, only a handful are necessary for combating C. difficile infections. The main bacterium in the gut responsible for infection prevention, as identified by mouse and human studies, is C. scindens. C. scindens normally functions to convert primary bile acids to secondary bile acids in the colon, using the enzyme 7a-hydroxysteroid dehydrogenase. When the researchers mutated the bacteria’s ability to produce 7a-hydroxysteroid dehydrogenase, C. difficile infection flourished in mice. The hypothesis was since C. difficile uses bile acids as an identifier of a hospitable environment, the conversion to secondary bile acids signals that the area is not safe for growth, and C. difficile moves on.
“Lots of people have looked at using bacteria to mediate the so-called colonization resistance to C. difficile,” said Vincent Young, a microbiologist and infectious disease physician at the University of Michigan, “but this paper really goes a long way towards defining a good mechanism for how it happens.” Indeed, the Food and Drug Administration has taken notice, granting the group approval to begin a Phase 2 clinical trial in bone marrow transplant patients. This trial will use an “autotransplantation” technique, whereby susceptible individuals will ingest their own stool in an effort to boost their C. difficile-fighting abilities, which also decreases the safety concerns of ingesting someone else’s fecal microbiome.
