A49 PRECLINICAL STUDIES OF TWO NOVEL LIVE BIOTHERAPEUTIC PRODUCTS FOR THE TREATMENT OF ULCERATIVE COLITIS
Bibliographic record
Abstract
Abstract Background The therapeutic approaches for ulcerative colitis present a high failure rate. Therefore, more therapeutic options are in the spotlight. Live biotherapeutic products, a more rationalized and tailored approach than probiotics, have a broader effect since they are not limited to a single therapeutic target. Aims To characterize the therapeutic effect of BioColoniz and BioPersist, two live biotherapeutic products derived from Lactobacillus reuteri and E. coli Nissle 1917, respectively, in rodent models of colitis. Methods To test the therapeutic effect of BioColoniz, 5 weeks old Muc2-/- mice, which spontaneously develop colitis, received a single dose of BioColoniz, L. reuteri or Vehicle via oral gavage; mice were monitored weekly until they showed clinical signs of disease and were euthanized. To evaluate the therapeutic effect of BioPersist, 6 weeks old C57BL/6 mice received BioPersist or vehicle via oral gavage, and then were exposed for 7 days to DSS for induction of acute colitis; parallel, mice received 5-ASA or vehicle daily. For both experiments, colons were collected and evaluated for macroscopic and histopathological changes. Results Mice treated with BioColoniz presented lower clinical scores, with a greater weight gain when compared to mice treated with L. retueri or vehicle. The appearance of rectal prolapse, a hallmark of the Muc2-/- model, was only recorded in mice treated with L. reuteri or Vehicle, supporting the protective effect of BioColoniz in the Muc2-/- model. Although the macroscopic analysis showed no changes in colon length among the groups, the histopathological analysis revealed decreased damage in mice treated with BioColoniz, significant when compared to mice who only received the vehicle. In order to evaluate if BioColoniz also protects against the development of comorbid metabolic defects of colitis, mice were also subjected to oral glucose tolerance test, finding that BioColoniz treated mice, especially males, display an improved glucose clearance when compared to L. retueri or vehicle groups. In the DSS model, BioPersist decreased daily clinical scores, significantly delaying the weight loss. The macroscopic analysis showed greater colon length in BioPersist treated mice than in mice treated only with 5-ASA, along with decreased histopathological damage. Conclusions Altogether, BioColoniz and BioPersist reduce the colitic phenotype in the Muc2-/- and DSS colitis models, respectively. Furthermore, BioColoniz protects Muc2-/- mice from the metabolic detriments of colitis. Future studies will focus on describing the mechanisms by which BioColoniz and BioPersist confer their therapeutic effect. Funding Agencies CCCMSFHR
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".