Boosting Good Bacteria Helps Body Fight C. difficile

Probiotic treatment is highly successful

Shaun Pinder

Shaun Pinder

Antibiotics are often the first line of defence against Clostridium difficile, a hospital-acquired infectious bacterium that causes severe diarrhea. U of G researchers are looking at new ways to combat the infection by boosting the body’s good bacteria instead of killing the bad ones. Antibiotics attack the disease-causing bacteria, but they also cause collateral damage to the friendly bacteria found in the intestinal tract. Overuse and misuse of antibiotics can also lead to antibiotic-resistant bacteria.

Another treatment option is to use a human probiotic infusion, which consists of a fecal transplant from a healthy donor that is administered to the patient as an enema mixed with saline. “It’s very cheap and has over a 92-per-cent success rate at curing C. difficile,” says Shaun Pinder, a master’s student in the Department of Mathematics and Statistics. “Instead of wiping out C. difficile, it acts to reconstitute all the good bacteria into your gut.”

Despite their high success rate, fecal transplants have a “gross factor,” says Pinder, and are used to treat severe cases of C. difficile infection only after antibiotics have failed. Fecal transplants aren’t always successful on the first try and may need to be repeated. Future tests may be able to predict which patients will require more than one treatment. C. difficile often strikes elderly people in poor health who go to the hospital and receive antibiotics, he adds. “There’s often a lot of confounding conditions,” says Pinder, which makes the elderly more vulnerable to infection.

Pinder is working with Dr. Christine Lee, who is doing a clinical trial on C. difficile patients at St. Joseph’s Hospital in Hamilton, Ont. Using stool samples from Lee’s patients, Pinder extracts bacterial DNA and sequences a specific gene that identifies bacteria in the samples before and after the infection. Gene sequencing gives researchers a bacterial population breakdown. “That sequence is so varied that you can identify different species by this gene,” says Pinder.

Instead of identifying individual species in Petri dishes, which can be time-consuming and ineffective, researchers can now use sequencing machines to analyze hundreds of thousands of species at a time. The study involved 20 patients, and each stool sample contained between 2,000 and 10,000 sequences.

“There’s so much data that you’re getting at the end of this project,” says Pinder. “You need to be able to deduce something from this huge data set. What exactly are the key relationships in this data set?” Dimension reduction techniques help sift through vast amounts of information by transforming the data into a smaller and simpler set of variables from which the most relevant details can be drawn.

Once the bacteria have been identified, the results will indicate how the patient’s microbial population has shifted from a normal to a diseased state. “We don’t really know what exactly a healthy state is and what exactly a diseased state looks like for every individual,” says Pinder. Probiotic treatments could be used to increase the number of good bacteria. Administered orally, probiotics are more palatable than fecal transplants and could be customized for the bacterial needs of each patient.

Prof. Emma Allen-Vercoe, Department of Molecular and Cellular Biology, has developed a “super-probiotic” called RePOOPulate as an alternative to human stool transplants. Unlike fecal matter, which may contain unknown pathogens, the super-probiotic consists of purified intestinal bacterial cultures.

Pinder did his undergrad in biomedical sciences at Guelph. “I’ve always been interested in health,” he says. A minor in statistics inspired him to use math in a health context. When he was looking for an adviser for his master’s degree, he met with Prof. Peter Kim, Department of Mathematics and Statistics, who was already working with Lee on the clinical trial. “I think more and more people will move away from antibiotics,” says Pinder. “It’s not good to wipe out all of your natural flora.”