Microbiome Profile is Distinct in Patients with Successful Response to Microbiota-Based Drug RBX2660 Relative to Placebo Responders
Bibliographic record
Abstract
Recurrent Clostridium difficile infections (rCDI) are associated with an altered microbiome composition and diversity compared with healthy patients. RBX2660, a standardized microbiota-based drug designed to rehabilitate patients’ microbiomes, was superior to placebo for preventing rCDI in a Phase 2B clinical trial (64% vs. 46% recurrence free at 56 days). Herein we assessed whether RBX2660 and placebo induced similar or different microbiome changes among patients classified as responders. Patients received blinded treatment of 2 doses of RBX2660 (Group A), 2 doses of placebo (Group B), or 1 dose of RBX2660 and 1 dose of placebo (Group C), with doses 7 days apart, and submitted stool samples at baseline, 7, 30, and 60 days after the second treatment. 16s rRNA analysis was performed on samples from 57 patients classified as responders (A, n = 21; B, n = 15; C, n = 21). Microbiome data for all patients at study entry were combined as a treatment-na•ve baseline. Groups A and C were pooled as “active” and compared with placebo treatments longitudinally. Microbiome divergence from baseline was determined with Kullback-Leibler (KL) analysis, mean group microbiomes and relative taxonomic abundance at the class level were determined using the Dirichlet-Multinomial distribution and compared with a generalized Wald-type test, and Shannon and Simpson diversity indices were compared with a two-sample Wilcoxon test. At 7, 30, and 60 days, microbiomes from RBX2660-treated patients had high KL divergence from baseline and significantly different means from baseline (P < 0.001). Placebo-treated patient microbiomes were less divergent from baseline, with group means significantly different from baseline at 7 and 60 days, but not 30 days. RBX2660 increased the relative abundances of Bacteroidia and decreased Gammaproteobacteria and Bacilli more than placebo. No significant differences in diversity indices were observed among treatment groups. RBX2660 treatment for rCDI is associated with greater changes in patient microbiomes than placebo treatment, underscoring the potential benefits of microbiome restoration therapy. Longer-term studies are needed to compare the durability of microbiome changes and recurrence-free rates. This analysis was funded by Rebiotix Inc., Roseville, MN. E. R. Dubberke, Rebiotix, Inc.: Scientific Advisor, Consulting fee; R. Orenstein, Rebiotix, Inc: Scientific Advisor, Consulting fee; C. Lee, Rebiotix, Inc.: Scientific Advisor, Consulting fee; S. Khanna, Rebiotix, Inc.: Scientific Advisor, Consulting fee; G. Hecht, Rebiotix, Inc.: Scientific Advisor, Consulting fee; D. N. Gerding, Rebiotix, Inc.: Scientific Advisor, Consulting fee; K. Blount, Rebiotix, Inc.: Employee, Salary; B. Shannon, Rebiotix, Inc.: Research Contractor, Consulting fee
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".