Bibliographic record
Abstract
Introduction: Gut microbiome has emerged as a potential driver of systemic immune checkpoint blockade (ICB) immunotherapy efficacy in various malignancies.Antibiotic (ATB) intake is known to modulate gut microbiota in a deleterious manner, potentially reducing the efficacy of ICB.We hypothesized that ATB intake prior to the initiation of intravesical bacillus Calmette-Guérin (BCG) immunotherapy, the gold-standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), may influence treatment response.Methods: We conducted a single-site, retrospective study of 622 NMIBC patients who received BCG immunotherapy at CHU de Québec from 2009-2019.ATB intake was collected from prescriptions and medical records up to 12 months prior to BCG initiation.Recurrence-free survival was evaluated using Kaplan-Meier analysis, and both uni-and multivariate Cox proportional hazards models were applied.We performed an in vivo experiment with C3H mice, which received a broad-spectrum ATB regimen either for one week or continuously.Mice were injected subcutaneously with MBT-2 bladder cancer cells and treated weekly with intratumoral BCG.To investigate the potential cause-effect relationship between the gut microbiome and BCG response, we performed fecal microbiome transfer (FMT) in the same bladder cancer mouse model pre-treated with ATB, using fecal samples collected at baseline from NMIBC patients who responded favorably or unfavorably to BCG.Results: Of the 622 NMIBC patients, 77 (12%) were exposed to ATB within three months before BCG initiation, while 545 (88%) were not.ATB-exposed patients showed a significantly reduced recurrence-free survival compared to unexposed patients (HR 1.96, 95% CI 1.36-2.83,p=0.0002).Fluoroquinolones were prescribed in over 70% of cases, and their combination with other antibiotics was associated with a shorter recurrence-free survival compared to fluoroquinolone alone or other ATB classes.In the mouse model, extended ATB treatment reduced the antitumor activity of BCG compared to control (p<0.01).FMT from nonresponder patients significantly reduced the antitumor efficacy of BCG compared to responder patients, suggesting that gut microbiota may influence BCG response.Conclusions: This large study demonstrates a detrimental effect of ATB intake within three months prior to BCG therapy in NMIBC patients.Preclinical data suggest that FMT and alterations in gut microbiota composition due to extended ATB intake may impair the antitumor efficacy of BCG, reinforcing the potential role of the microbiome in modulating the response to BCG immunotherapy.These findings underscore the importance of judicious ATB prescribing practices prior to BCG initiation to potentially optimize NMIBC treatment outcomes and enhance BCG efficacy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.336 | 0.157 |
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 source (direct Gemma or distilled Codex), 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".