Dysbiosis, or disruption of a healthy microbiome, is strongly associated with Clostridium difficile infections (CDI)
There are several clinical development programs in progress to develop FDA approved microbiome-based drugs. However, quantitative biomarkers for microbiome dysbiosis and/or restoration have not been established.
In a recent Phase 2 open-label trial, a single dose of RBX2660, a standardized microbiotabased product, performed significantly better than historical controls. Microbiome analysis indicated that RBX2660 restored a healthier microbiome, as defined by the RBX2660 product profile and the Human Microbiome Project (HMP).
Herein, we outline and evaluate a unidimensional index, the Microbiome Health Index (MHI), that describes microbiome rehabilitation among patients from that Phase 2 open-label trial.
Included in this analysis are 47 RBX2660 product samples and 254 stool samples collected at the indicated time points from 122 patients with recurrent CDI who received at least one dose of RBX2660 as part of the PUNCH Open Label Phase 2 trial (NCT02589847). Success was defined as the absence of CDI at 8 weeks after the last blinded treatment.
Stool samples were sequenced using BoosterShot (CoreBiome, Minneapolis, MN), an ultra-shallow shotgun sequencing that generates taxonomic profiles with species level resolution.
MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project. MHI significantly increases at 10 days after treatment among RBX2660 responders. This outcome is consistent with MHI results from a prior RCT of RBX2660 for rCDI.
Future efforts will determine whether more specific taxonomic characterization below the class level and/or inclusion of diversity metrics provide a more precise index. Also, we will evaluate MHI prospectively in ongoing clinical trials as an exploratory endpoint.