A49 TWO NOVEL LIVE BIOTHERAPEUTIC PRODUCTS PROTECT DSS-EXPOSED MICE FROM ACUTE COLITIS WHEN COMPARED TO 5-ASA
Bibliographic record
Abstract
Abstract Background Live biotherapeutic products (LBPs) offer a more rationalized and multitargeted approach to treating gastrointestinal diseases. BioColoniz and BioPersist are two LBPs derived from the parental strains L. reuteri and E. coli Nissle 1917 (EcN), respectively. The parental strains are known to offer some benefit in preventing relapses in IBD patients however the results are heterogeneous. To overcome this, the parental strains were approached as LBPs by introducing traits to thrive under the inflammatory conditions of the colon. Therefore, our aim is to characterize the role of these LBPs in IBD. Purpose To evaluate the therapeutic effect of the LBPs BioColoniz and BioPersist in an acute model of colitis. Method Female C57Bl/6 mice were treated with BioColoniz or BioPersist via oral gavage for three consecutive days prior to DSS challenge. Then mice were exposed to 3.5% DSS via drinking water for seven days. As controls, we also included mice treated with vehicle or the parental strains L. reuteri or EcN. In order to compare the effect of LBPs in the onset of acute colitis to current maintenance therapies for UC, we also exposed another group of mice to DSS and simultaneously administer 5-ASA. Mice were monitored daily for signs of disease and at the end of the experiment, colon tissue was collected for histopathological and molecular analysis. Result(s) The administration of BioColoniz and BioPersist delayed and decreased the colitic phenotype of mice exposed to DSS. Differences in signs of disease, such as diarrhea and weight loss, were evident by day 4 for vehicle or 5-ASA groups, whereas mice in the LBPs groups were still gaining weight. When analyzing the histopathological changes, mice in the LBPs groups presented lower scores when compared to the vehicle and 5-ASA groups. Specifically, mice treated early with BioColoniz or BioPersist presented a more preserved mucosal architecture with visible crypts. Although 5-ASA-treated mice still had vestiges of crypts, the damage in the mucosal architecture was more severe, similar to the observed in mice treated with the parental strains EcN and L. reuteri. We also looked at the expression of proinflammatory cytokines, finding an increase in TNFα, IFNγ, and IL-17a in mice treated with 5-ASA but not in mice treated with LBPs. However, the expression of protective factors such as mucin Muc2 or the antimicrobial peptide Reg3γ was similarly high in 5-ASA and LBP-treated mice when compared to vehicle or parental strains groups, suggesting some therapeutic commonalities between 5-ASA and our LBPs. Conclusion(s) The early administration of the LBPs BioColoniz and BioPersist protect mice from severe acute colitis, being more protective than 5-ASA. Since some differences and similarities were observed between the LBPs- and 5-ASA-treated mice, such as crypt preservation versus increased expression of some protective factors, the next step will aim to identify which mechanisms are specifically triggered by the LBPs. Disclosure of Interest None Declared
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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 | 0.000 | 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) | 0.000 | 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".