Bacteria in the human gut microbiome maintain a delicate balance, where beneficial bacteria keep potentially harmful microbes in check. Antibiotic treatment can disrupt this harmony, allowing pathogens like Clostridium difficile to wreak havoc, causing diarrhea, stomach cramps, and colon inflammation. Antibiotics also deplete the healthy microbiome, which paves the way for reinfection. Infection recurrences are difficult to treat, with one recurrence increasing the risk of repeated reinfections.
In the past decade, researchers have shown that transplanting fecal material from healthy donors can prevent recurrent C. difficile infections. However, this procedure is not without risks.
“To a certain extent, a fecal transplant is almost like going to the pharmacist where they take a little bit of everything off the shelf and put it into one pill, assuming that something will probably help,” said Jordan Bisanz, a biochemist and molecular biologist at The Pennsylvania State University, in a press release. “But we don’t know 100 percent what’s in there.”
Now, in research published in Cell Host & Microbe, Bisanz and his colleagues have identified which gut bacteria can suppress C. difficile infections, laying the foundation for probiotic-based strategies as an alternative to antibiotics and fecal microbiota transplants.
Bisanz and his team started out by investigating C. difficile’s “friends,” microbes that coexist with it, and its “enemies,” those that may suppress the bacterium. They performed a meta-analysis of previously published studies containing information about C. difficile load in people alongside gut microbiome sequencing data. With the help of machine learning, they identified 25 bacterial strains that cooccurred with C. difficile, and 37 strains that were negatively correlated with its presence.
The researchers then created a community of bacteria by coculturing the 37 strains negatively linked to C. difficile. Treating a C. difficile culture with this synthetic version of a fecal microbiota transplant (sFMT) reduced its growth. When the researchers exposed sFMT-colonized mice to C. difficile, the animals had significantly less weight loss and toxin abundance compared to control mice that received bacteria-free media.
To investigate whether a sFMT protected mice from antibiotic-induced C. difficile reinfection, the researchers treated mice with an antibiotic, infected them with C. difficile, and then treated them with another antibiotic before subjecting them to a sFMT. Compared to controls, sFMT-treated mice showed delayed infection relapse and reduced disease severity.
By Sneha Khedkar
Article can be accessed on: The Scientist