A team of researchers is exploring the possibility that next–generation probiotics would reduce the risk of infection with Clostridium difficile. In laboratory–grown bacterial communities, the researchers determined that, when supplied with glycerol, the probiotic Lactobacillus reuteri produced reuterin, an antibacterial compound that selectively killed C. difficile.

The study appeared in the journal Infection and Immunity.

“Although most patients respond to antibiotic treatment, up to 35 percent will relapse and require extended antibiotic treatments,” said first and corresponding author Dr. Jennifer K. Spinler, instructor of pathology & immunology at Baylor College of Medicine, who oversees microbial genetics and genomics efforts at the Texas Children's Microbiome Center at Texas Children’s Hospital.

“When repeated antibiotic treatments fail to eliminate C. difficile infections, some patients are resorting to fecal microbiome transplant – the transfer of fecal matter from a healthy donor – which treats the disease but also could have negative side effects,” Spinler said. “We wanted to find an alternative treatment, a prophylactic strategy based on probiotics that could help prevent C. difficile from thriving in the first place.”

Working in the Texas Children’s Microbiome Center, Spinler and her colleagues tested the possibility that probiotic L. reuteri, which is known to produce antibacterial compounds, could help prevent C. difficile from establishing a microbial community in lab cultures.

The Britton lab uses mini–bioreactor arrays – multiple small culture chambers – that provide a platform in which researchers could recreate the invasion of an antibiotic–treated human intestinal community by C. difficile.

“Using the mini–bioreactors model we showed that L. reuteri reduced the burden of C. difficile infection in a complex gut community,” Britton said. “To achieve its beneficial effect, L. reuteri requires glycerol and converts it into the antimicrobial reuterin.”

The literature reports reuterin as a broad–spectrum antibiotic; it affects the growth of a wide variety of bacteria when they are tested individually in the lab. What was intriguing in this study is that reuterin didn’t have a broad–spectrum effect in the mini–bioreactor bacterial community setting.

“I expected reuterin to have an antibacterial effect on several different types of bacteria in the community, but it only affected C. difficile and not the good bacteria, which was exciting because it has major implications for a preventative strategy,” Spinler said.

“Although these results are too preliminary to be translated directly into human therapy, they provide a foundation upon which to further develop treatments based on co–administration of L. reuteri and glycerol to prevent C. difficile infection,” said co–author Dr. Jennifer Auchtung, director of the Cultivation Core at Baylor’s Alkek Center for Metagenomics and Microbiome Research and assistant professor of molecular virology and microbiology at Baylor.

In the future, this potential treatment could be administered prophylactically to patients before they take antibiotics known to disrupt normal gut microbes. The L. reuteri/glycerol formulation would help maintain the healthy gut microbial community and also help prevent the growth of C. difficile.