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Fecal Microbiota Transplantation via Colonoscopy for Recurrent C. difficile Infection
Published on: December 8, 2014
Cohesive modules of engraftment in fecal microbiota transplantation
Armin Rashidi1,2, Samuel S Minot3, Stephanie J Lee1,2
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Abstract:
While single-strain probiotics fail to address community-level microbiota injuries in dysbiosis-related conditions and fecal microbiota transplantation (FMT) produces unpredictable communities, a middle-ground approach has emerged. This approach involves using small consortia of species, combining the precision of single-strain probiotics and the holistic approach intrinsic to FMT. The species selection in this oligomicrobial strategy is typically proprietary or based on studies linking single species to disease or health. To advance this approach, we developed the concept of cohesive modules of engraftment (CME) and a workflow for their identification from FMT trials. CMEs represent small donor microbiota subsets that engraft as units (modularity), while maintaining their original composition (cohesiveness). In benchmarking, we identified >200 highly cohesive CMEs (2-5 species) in 5 FMT trials and found evidence for cross feeding as a mechanism for CME integrity. Due to their predictable post-treatment compositions, CMEs deserve investigation as potential ingredients of future therapeutic microbial consortia.
Insights
Researchers identified cohesive modules of engraftment (CME) from fecal microbiota transplantation (FMT) trials. These small, stable microbial communities show promise for developing predictable, next-generation therapeutic microbial consortia.
Area of Science:
- Microbiology
- Gastroenterology
- Systems Biology
Background:
- Single-strain probiotics have limited efficacy for complex microbiota injuries in dysbiosis.
- Fecal microbiota transplantation (FMT) can restore gut microbiota but often results in unpredictable community compositions.
- Oligomicrobial strategies, using small defined consortia, offer a potential middle-ground between single strains and FMT.
Purpose of the Study:
- To develop a method for identifying stable, engraftable microbial subsets from FMT data.
- To introduce the concept of cohesive modules of engraftment (CME) as predictable units within the microbiota.
- To evaluate CMEs as potential building blocks for future therapeutic microbial consortia.
Main Methods:
- Developed a workflow to identify cohesive modules of engraftment (CME) from fecal microbiota transplantation (FMT) trial datasets.
- Analyzed data from five FMT trials to identify and characterize CMEs.
- Investigated potential mechanisms, such as cross-feeding, that maintain CME integrity.
Main Results:
- >200 highly cohesive CMEs, comprising 2-5 species, were identified across five FMT trials.
- Evidence suggests that cross-feeding interactions are crucial for maintaining the cohesiveness and integrity of CMEs.
- CMEs demonstrated predictable compositions post-treatment, indicating modular engraftment.
Conclusions:
- Cohesive modules of engraftment (CME) represent stable, predictable subsets of the gut microbiota that engraft as units.
- CMEs, identified through a novel workflow from FMT trials, offer a promising strategy for developing defined microbial therapeutics.
- The predictable nature of CMEs makes them ideal candidates for future precision microbial consortia development.
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