Inspired by human fecal transplants this new microbiome therapy restores gut balance without using fecal matter. Instead it relies on a select group of bacterial strains known to suppress C. difficile. In mice it matched the effectiveness of fecal transplants while reducing safety concerns.

The gut microbiome typically maintains balance, preventing harmful bacteria from overgrowing. While many people carry C. difficile without issue, antibiotics can disrupt this balance by eliminating beneficial bacteria, allowing C. difficile to thrive. It is responsible for 15–25% of antibiotic-associated diarrhea and often emerges after hospital visits.

Treating C. difficile infections is particularly difficult since the bacteria are drug-resistant and antibiotics further disturb the microbiome leading to recurring infections. According to the CDC, C. difficile causes 500,000 infections annually and contributes to $1.5 billion in U.S. healthcare costs.

Fecal microbiota transplants have proven effective in restoring gut balance but they come with risks. It’s like picking a little of everything off the shelf and hoping something works said senior author Jordan Bisanz noting that the exact composition is unknown and could contain harmful bacteria.

Instead of using a random mix the researchers aimed to pinpoint bacteria that actively suppress C. difficile and reconstruct a targeted lab-designed microbiome therapy. By analyzing data from 12 published studies they used machine learning to identify microorganisms that either co-occur with C. difficile or inhibit its growth creating a precision-based alternative to fecal transplants.

The researchers identified 37 bacterial strains that were negatively correlated with C. difficile meaning their presence prevented infection and 25 strains that were positively correlated appearing alongside C. difficile infections. Using this data, they formulated a synthetic microbiome therapy by combining bacteria that suppressed C. difficile, creating a lab-designed alternative to fecal transplants.

Tested in vitro and administered orally to mice the therapy significantly reduced C. difficile growth resisted infection and was as effective as traditional fecal transplants. It also protected against severe disease delayed relapse and reduced recurrent infection severity. Further experiments revealed that a single bacterial strain was key to C. difficile suppression alone it was as effective as a fecal transplant in preventing infection in mice.

If you have this Peptostreptococcus strain, you don’t have C. difficile it’s a powerful suppressor, even more effective than all 37 strains combined said Jordan Bisanz. He explained that this bacterium excels at consuming proline an amino acid essential for C. difficile growth. While previous studies emphasized secondary bile acid metabolism as key to C. difficile resistance these findings suggest proline competition may play a larger role opening new possibilities for treatment.

Bisanz noted that this approach to microbiome science could help unravel host-microbial interactions in conditions like inflammatory bowel disease paving the way for new therapies. The goal is to develop microbes as targeted drugs and treatments he said.

Source: https://www.psu.edu/news/research/story/synthetic-microbiome-therapy-suppresses-bacterial-infection-without-antibiotics