Researchers at Penn State have developed a synthetic microbiome therapy that protects mice from severe symptoms of a difficult-to-treat and potentially life-threatening gut infection. The therapy targets Clostridioides difficile a bacterium known to cause severe diarrhea abdominal pain, and colon inflammation often thriving when the gut microbiome is disrupted. The findings suggest this approach could lead to new probiotic treatments for C. difficile infections as an alternative to antibiotics and traditional fecal microbiota transplants.

Unlike conventional fecal transplants which involve transferring bacteria from a healthy donor’s stool to restore microbiome balance this new therapy eliminates the need for fecal matter. Instead it utilizes a select group of bacterial strains specifically linked to C. difficile suppression. In mice it proved just as effective as fecal transplants while posing fewer safety concerns.

We need to take a much more targeted approach to microbiome interventions said senior author Jordan Bisanz assistant professor of biochemistry and molecular biology and the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Host-Microbiome Interactions.

In a healthy microbiome microbial organisms regulate each other preventing harmful overgrowth. While many individuals carry C. difficile in their gut without  issues antibiotics can disrupt this balance by eliminating beneficial bacteria alongside harmful ones creating an environment where C. difficile thrives. The bacterium is responsible for 15% to 25% of antibiotic-associated diarrhea with infections often occurring after hospital or healthcare facility visits.Treating C. difficile infections is challenging as the bacteria are drug-resistant and antibiotics further disrupt the gut microbiome leading to recurrent infections.

The CDC reports 500,000 infections and $1.5 billion in healthcare costs annually in the U.S. Fecal microbiota transplants can restore gut balance but carry risks as their contents are not fully known. Researchers questioned whether a more precise approach could be developed by identifying bacteria that best suppress C. difficile. They aimed to reconstruct a targeted microbial therapy in the lab as a safer alternative to fecal transplants.The researchers aimed to transform microbiome science into precision therapies eliminating the need for fecal transplants. They analyzed 12 studies using machine learning to identify bacteria that either suppressed or coexisted with C. difficile.

By combining 37 strains linked to C. difficile suppression they created a synthetic microbiome therapy. When tested in mice the treatment effectively reduced C. difficile growth prevented infection and matched the effectiveness of traditional fecal transplants.Through experiments researchers identified a single bacterial strain Peptostreptococcus as key to suppressing C. difficile proving as effective as a human fecal transplant. This strain outperformed the 37-strain combination by depriving C. difficile of proline an essential amino acid for its growth. The findings suggest proline competition plays a larger role in resistance than previously thought opening new therapeutic possibilities. The team’s approach could also help understand host-microbial interactions in diseases like inflammatory bowel disease. The study was supported by multiple NIH institutes Penn State’s Biochemistry and Molecular Biology Department and the Huck Institutes of the Life Sciences.

Sourcr: https://science.psu.edu/news/synthetic-microbiome-therapy-suppresses-bacterial-infection-without-antibiotics