Can a 15-strain microbiome therapy replace fecal transplant?

Clinical Takeaway: In patients with recurrent C. difficile infection, a 15-strain live biotherapeutic product (LBP) demonstrated safety and preliminary efficacy comparable to fecal microbiota transplant (FMT), supporting further development of defined, scalable microbiome therapies.

Fecal microbiota transplant (FMT) is effective for recurrent Clostridioides difficile infection (rCDI) but remains difficult to standardize and scale. A manufactured, defined bacterial consortium could offer a more reproducible and accessible microbiome-based treatment option.

A randomized phase 1b trial compared a manufactured 15-strain LBP with FMT derived from the same donor source in 18 adults with recurrent C. difficile infection. Participants were randomized into four small groups (n=4–5 each): low- and high-dose LBP and low- and high-dose FMT, delivered via colonoscopy.

Across treatment arms, both LBP and FMT were well tolerated, with no major safety signals reported. Clinical responses were broadly similar between groups, with most patients achieving resolution of recurrent infection after treatment; efficacy appeared comparable across dose levels in this small cohort. Microbiome analyses showed that bacterial strains present in both interventions successfully engrafted in recipients, with durable persistence observed over time.

Notably, the LBP consists of a defined consortium of 15 bacterial strains isolated from donor stool and grown under controlled, Good Manufacturing Practice-compliant conditions—enabling reproducibility and quality control not feasible with traditional stool-based FMT. This platform represents a step toward standardized microbiome therapeutics that can be manufactured at scale.

“We demonstrated comparable safety and efficacy between undefined stool-based FMT and a defined, in vitro-manufactured LBP,” said co-senior author Jeremiah J. Faith, PhD. “We also found that bacterial strains delivered through both FMT and LBP durably engrafted in recipients.”

Although limited by small sample size and phase 1b design, these findings support further trials to confirm efficacy, optimize dosing, and explore broader applications. An oral formulation of the LBP is also in development, which could further improve patient access and convenience.

Source: Bethlehem L, et al. (2026, June 2). Nat Med. 15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial