C. difficile, a major cause of antibiotic-associated diarrhea, is suppressed by the gut microbiome, but the precise mechanisms are not fully described. Through meta-analysis of 12 human studies, we designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization. This lab-built 37-strain consortium formed a functional community suppressing C. difficile in vitro and in animal models. Using sFMT1 as a tractable model system, we find that bile acid 7⍺-dehydroxylation is not a determinant of sFMT1 efficacy while a single strain performing Stickland fermentation, a pathway of competitive nutrient utilization, is both necessary and sufficient for suppression of C. difficile replicating the efficacy of a human fecal transplant in a gnotobiotic mouse model. These studies demonstrate a generalizable pipeline merging big data approaches with reductionist experimental models for the mechanistic interrogation of complex microbial communities.

About the speaker
Jordan Bisanz, Assistant Professor of Biochemistry and Molecular Biology
Pennsylvania State University
Jordan Bisanz is an Assistant Professor of Biochemistry and Molecular Biology at Pennsylvania State University and the One Health Microbiome Center. The Bisanz lab combines computational analyses and wet lab experimentation to understand how gut microbes interact with each other and their host. The lab specializes in coupling human intervention studies with multi ‘omics approaches and gnotobiotic models to understand how host-microbe interactions shape health, generating both mechanistic insights and translational targets.
Date of recording:Wednesday, March 13, 2024
Duration:60 minutes
Next Generation Sequencing