A154 DIRECT BACTERICIDAL EFFECT OF PANTOPRAZOLE ON BACTERIAL ISOLATES FROM THE GUT MICROBIOME
Bibliographic record
Abstract
Proton pump inhibitors (PPIs) block the H+,K+-adenosine triphosphatases, inhibiting gastric acid secretions and raise the pH of the gastrointestinal tract (GI). PPI use had been associated with a 2-fold increased risk in developing Clostridium difficile disease, an infection that is strongly linked to disruptions in microbial communities of the GI tract. Although, PPI use has been associated with increased C. difficile infection, the mechanism by which this occurs is unclear. Recent reports have suggested that PPI’s directly influence bacterial populations in the host microbiome. Here we investigate the direct impact of pantoprazole on a defined microbial community (MET-1) consisting of 33 bacterial species isolated from healthy human stool using a continuous culture model that emulates the human distal colon. Investigate the direct impact of pantoprazole on the community dynamics of MET-1. To examine the direct impact of PPIs on bacteria, pantoprazole was incubated with individual bacterial species found in MET-1 at 5, 50, 500 and 5000 ug/mL for 24 hrs at 37oC. To examine the impact of pantoprazole on a microbial community as seen in the GI tract, a physiologic concentration of pantoprazole (40 mg/ 12 hours for 10 days) was added to a continuous culture system of MET-1 at steady state (37°C, pH 6.8 grown under anaerobic conditions). Levels of acid (HCl), base (NaOH) consumption and microbial growth and viability were monitored using optical density and flow cytometry. Growth inhibition to pantoprazole on individual members of MET-1 was concentration dependent and was more pronounced in some community members. Bifidobacterium adolescentis and Eubacterium ventriosum were sensitive at 5ug/ml (OD decrease 22.71% and 22.37% compared to control, p<0.05), while Dorea longicatena and Escherichia coli exhibited growth inhibition at 50ug/ml (OD decrease 13.59 and 9.26% compared to control, p<0.05), both of which are biologically relevant concentrations of pantoprazole. Pantoprazole exposure in a continuous culture system of MET-1 was associated with a significant decrease in bacterial density (12%, p<0.001 compared to control) and bacterial viability within three days of pantoprazole initiation. These results suggest that pantoprazole have a direct impact on the bacterial growth and viability of both individual bacteria and microbial communities in a short period of time. Sensitivity to PPIs of keystone bacterial species in the gastrointestinal tract including Bifidobacterium and Eubacterium may be linked to the observed increased risk in development of Clostridium difficile disease as well as affecting the homeostasis in the GI tract. None
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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 | 0.000 | 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 | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".