A163 INFECTION WITH HYMENOLEPIS DIMINUTA ELICITS A TH2 IMMUNITY AND ALLEVIATES DNBS-COLITIS IN A MOUSE MODEL WITH MINIMAL INTESTINAL MICROBIOTA
Bibliographic record
Abstract
Abstract Background Immunocompetent mice infected with the rat tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic-acid (DNBS)-induced colitis that was accompanied by the increased relative abundance of short-chain fatty acid (SCFA)-producing bacteria and fecal SCFA levels at 8 days post-infection (dpi). These changes were not observed in antibiotic-treated BALB/c mice or germ-free mice. To further characterize the host-parasite-microbiota interaction in the control of colitis, experiments have been conducted in a reductionist system in which the H. diminuta anti-colitic response was tested in mice colonized with 12 commensal bacteria representing the major five phyla of the mouse gut. Purpose To identify key bacterial species and microbe-derived mediators involved in the H. diminuta-induced protection from DNBS-induced colitis. Method OligoMM12 (Oligo-Mouse-Microbiota) mice (n=4-8/group) were infected with 10 viable antibiotic-treated H. diminuta cysticercoids eight days prior to challenge with DNBS (3mg, i.r.). Mice were monitored daily and necropsied 72h post-DNBS. Disease was assessed by a macroscopic disease activity score, colon length and histopathology on H&E sections of mid-colon. Production of IL-4, -5, -10 and -13 by concanavalin-A treated spleen cells by ELISA was used as an index of successful helminth infection. Result(s) OligoMM12 mice treated with DNBS developed acute colitis, with 3/8 mice requiring humane euthanization, while all mice infected with H. diminuta survived the DNBS challenge. Successful infection was confirmed by statistically significant increases in splenic output of the Th2-cytokines in response to mitogenic stimulation and efficient expulsion of the worms burden by 11 dpi. The severity of DNBS-induced colitis was reduced in H. diminuta-infected mice (n=4), although additional experiments are required to confirm the statistical significance of these data. Conclusion(s) Reproducible DNBS-induced colitis in mice with the simplified OligoMM12 consortium of bacteria and reduced disease in H. diminuta-infected mice has created a model by which the participation of exact bacterial groups or species in H. diminuta-induced suppression of colitis can be tested. This is of translational value, since the failure of helminth therapy in IBD could be predicated by dysbiosis in the patient, and therefore potentially overcome by combination therapy of ‘probiotic’ and helminth. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; NSERC-CGS D, Eyes High doctoral Recruitment Scholarship Disclosure of Interest None Declared
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".