Researchers at the Icahn School of Medicine at Mount Sinai have developed a new manufacturing platform to produce a targeted mixture of beneficial gut bacteria. This approach could help expand access to microbiome-based treatments for patients with relapse. clostridioides difficile (C. difficile) infection.
Their findings were published in the June 2 issue of the journal. natural medicine (10.1038/s41591-026-04442-2).
recurrent C. difficile Infections are serious and often debilitating conditions that can occur after antibiotic treatment disrupts the natural balance of bacteria in the intestines. Fecal microbiota transplantation (FMT), a treatment that transplants stool from healthy donors to restore gut bacteria in patients with severe or recurrent infections, has proven effective in many patients, but more standardized and scalable treatment options are needed.
To address this challenge, researchers have developed a cost-effective production platform that can produce live biotherapeutic products (LBPs) that are composed of known bacterial strains rather than whole fecal material.
The first products generated using this platform were evaluated in patients with recurrent disease. C. difficile Infection was examined and directly compared with FMT prepared from the same donor source used to isolate the bacterial strain.
In a direct Phase 1b clinical study led by co-senior author and co-corresponding author Ari Grinspan, MD, the team compared treatment using the new platform microbiome to treatment using FMT. The study enrolled 18 participants across four groups: low-dose and high-dose FMT, low-dose and high-dose LBP, with 4 to 5 patients in each group.
Microbiome therapy has shown great potential, but manufacturing challenges have delayed widespread clinical use. We wanted to create a practical and scalable method to produce defined bacterial therapeutics that can be consistently manufactured and rigorously tested. And we defined for the first time an undefined stool-based FMT, in vitro・Made by LBP. We also found that bacterial strains delivered through both FMT and LBP permanently engrafted in the recipient. ”
Dr. Jeremiah J. Faith, co-senior author and co-corresponding author, Professor of Immunology and Immunotherapy, Genetics and Genomic Sciences, and Medicine, Icahn School of Medicine at Mount Sinai
The new approach uses a defined consortium of bacterial strains isolated from donor stool and grown under controlled manufacturing conditions. Unlike traditional fecal microbiota transplants, which can vary from donor to donor, this platform is designed to generate standardized microbial therapies at scale, the researchers said.
“Our goal was to move beyond stool-based treatments to more accurate and reproducible treatments,” says Dr. Grinspan, assistant professor of gastroenterology and director of gastrointestinal microbial therapeutics at the Icahn School of Medicine at Mount Sinai. “By defining precisely which bacterial strains are involved, we can better understand how these treatments work and potentially improve safety, quality control, and scalability.”
The researchers say their findings support the feasibility of producing defined microbiome therapeutics that could one day provide a more standardized alternative to traditional fecal microbiota transplants.
“Our study represents an important step toward industrial-scale microbiome therapy,” says Dr. Faith. “We believe that defined live biotherapeutic products will help make these treatments more accessible while preserving the therapeutic benefits seen in donor-derived microbiota.”
The authors note that additional studies are needed to further evaluate the long-term efficacy, safety, and broader clinical application of this platform.
Next, the researchers plan to use this platform to develop and test LBPs against additional inflammatory and infectious diseases. They also aim to accelerate the translation of microbiome science into clinical care by making the platform technology available to other researchers working on live microbial treatments.
The 15-strain consortium in this study was administered by colonoscopy, but the researchers subsequently developed an oral formulation designed to provide a more convenient delivery method in future clinical studies.
The drug was manufactured by lead author Dr. Lucas Bethlehem, a former postdoctoral fellow in Dr. Faith’s lab, using a custom-built anaerobic (oxygen-free) chamber designed for Good Manufacturing Practice (GMP) production of live biotherapeutic products, a quality standard required for pharmaceutical manufacturing.
sauce:
Mount Sinai Health System
Reference magazines:
Bethlehem, L. Others. (2026). 15-strain live biologic or same-donor fecal microbiota transplantation for recurrent Clostridioides difficile infections: a randomized phase 1b trial. natural medicine. DOI: 10.1038/s41591-026-04442-2. https://www.nature.com/articles/s41591-026-04442-2
