Clinical trial finds comparable safety, efficacy, and long-term bacterial engraftment between a defined 15-strain microbial therapy and traditional fecal microbiota transplantation

Researchers have reported promising results from a clinical trial evaluating a standardized, laboratory-manufactured microbial therapy as a potential alternative to fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI).

FMT has become an effective treatment for patients suffering from recurrent C. difficile infections, a serious condition that often develops after antibiotic use disrupts the gut’s natural microbial balance. However, widespread adoption of FMT has been limited by challenges related to donor variability, manufacturing consistency, regulatory oversight, and scalability.

To address these limitations, investigators developed a novel production platform capable of manufacturing live biotherapeutic products (LBPs) composed of defined bacterial strains isolated from healthy donor stool and grown under controlled laboratory conditions. The first therapy produced using this platform, known as MTC01, contains a consortium of 15 bacterial strains designed to restore microbial diversity in the gut.

In a randomized Phase 1b clinical trial, researchers directly compared MTC01 with conventional FMT prepared from the same donor source used to isolate the bacterial strains. The study enrolled 18 patients with recurrent C. difficile infection, who were assigned to one of four treatment groups: low-dose FMT, high-dose FMT, low-dose MTC01, or high-dose MTC01.

The trial met its primary safety endpoint. Researchers reported 10 adverse events among eight participants, evenly distributed between the FMT and MTC01 treatment groups. No treatment-related adverse events were observed.

The study also demonstrated comparable efficacy between the two approaches. Eight weeks after treatment, recurrent infection was prevented in seven of nine patients receiving MTC01 and in eight of nine patients receiving FMT. Additionally, bacterial strains successfully engrafted and persisted in recipients over time in both groups, with higher doses of MTC01 associated with greater strain engraftment.

“We demonstrated comparable safety and efficacy between undefined stool-based FMT and a defined, in vitro-manufactured live biotherapeutic product,” the investigators reported. “We also found that bacterial strains delivered through both FMT and LBP durably engrafted in recipients.”

Researchers note that, unlike traditional stool-based transplants, the manufacturing platform enables production of microbial therapies with a defined composition and greater consistency. The team has also made regulatory documentation and manufacturing protocols available to help accelerate the development and clinical evaluation of future microbiome-based therapies.

The findings represent an important step toward the development of standardized microbiome therapeutics that could eventually complement or replace donor-derived fecal transplants. While current products contain a relatively small number of bacterial strains, advances in microbial cultivation and manufacturing technologies may enable increasingly complex and precisely engineered microbial communities in the future.

The study’s authors conclude that scalable, defined microbiome therapies have the potential to overcome key limitations of traditional FMT while maintaining therapeutic effectiveness, paving the way for broader clinical use of microbiome-based treatments.