Employing ‘good’ bacteria
Trevor Lawley from the Wellcome Trust Sanger Institute explains how he’ll be identifying the good bacteria in faeces that can cure patients with persistent Clostridium difficile infection in the third of a mini-series of posts from recipients of MRC Centenary Awards.
History is littered with examples of people deliberately infecting themselves in the name of science. Volunteers have been known to drink norovirus-infected water to see how long the virus can survive. A Russian researcher reportedly identified Hepatitis E by making himself a meal of yoghurt mixed with the stool of six ill soldiers. And the Australian researcher Barry Marshall won a Nobel prize for his work showing that the bacteria Helicobacter pylori caused stomach ulcers after drinking a petri dish of the cultured bacteria.
But what about infecting yourself with one microbe to treat another? My research focuses on the bacterium Clostridium difficile and I’m hoping that we can infect patients with ‘good’ bacteria to treat it.
C. difficile often lives harmlessly in the gut microbial ecosystem, but if the good bacteria that keep it in check are wiped out — by antibiotics, for example — it can grow rapidly, causing severe diarrhoea and dangerous inflammation of the gut. Other diseases, such as ulcerative colitis and Crohn’s disease, can also result from imbalances in this delicate ecosystem.
One treatment option is a ‘whole faecal’ transplant, where doctors transplant faeces from a healthy donor into a person ill with C. difficile by an enema, through a nasogastric tube or a colonoscopy.
This kind of transplant cures more than 90 per cent of C. difficile infections. But it’s not a particularly practical treatment — it takes time to identify someone to donate their gut bacteria, the procedure might introduce other less-welcome microbes, and, perhaps understandably, it’s not something that patients are particularly enthusiastic about. As a result this promising treatment remains on the fringe of modern clinical practice.
Our aim is to create a treatment where doctors transplant a handful of known bacteria that have been cultured in the lab. We’ve already done this in mice — in research published today in PLoS Pathogens we showed that six species of bacteria taken from the guts of healthy mice cured C. difficile infections in the animals.
Now we want to do that in humans. With our Centenary Award we intend to continue looking at bacteria from healthy people’s guts to identify those that might be best for treatment. We’ve become pretty good at culturing bacteria from mice in the lab and now we’re extending that to bacteria from human guts.
Once we’ve defined the human bacteria to use, they could then be tested in patients by encapsulating the bacteria in a pill form and asking the patients to swallow them.
We won’t be ready to try the treatment in humans by the time the Centenary funding runs out — human tests are still around two to three years away — but I do hope that we’ll have a clearer picture of which bacterial groups might be good to test by the time the funding ends.
That’ll put us in a much stronger position to apply for funding to continue the project, and put us a little closer to using ‘good’ bacteria to fight the ‘bad’ bacteria in our guts.
The MRC Centenary Awards have been provided to the very best MRC-funded early-career researchers to give them extra time and resources to build on their achievements and learn new skills. £14m was made available for the awards, which mark 100 years of the MRC in 2013.