A183 SUCCINATE IN THE RELATIONSHIP BETWEEN INFLAMMATORY BOWEL DISEASE AND OBESITY IN SUCCINATE RECEPTOR DEFICIENT MICE
Bibliographic record
Abstract
Abstract Background The incidence of Inflammatory Bowel Disease (IBD) among the obese pediatric populations is increasing. Succinate has been identified as a possible metabolite linking the two diseases. Succinate receptor 1 (SUCNR1) gene knockout (KO) mice are less susceptible to dextran sulfate sodium (DSS)-induced colitis. Aims To determine whether succinate plays a role in mice becoming obese and colitis in obesity, and whether an obese-inducing diet would change the gut microbiota. We hypothesized that SUCNR1-KO mice would not become obese and would experience less colonic inflammation despite the diet. Methods C57BL/6 (WT) were bred with SUCNR1-KO mice (generously provided by Amgen), and the heterozygous (HZ) F1 offspring bred to obtain F2. Two of 3 F2 litters included SUCNR1-KO mice, which were caged by sex but not genotype. These F2 mice began a high-fat/high-sugar (obese, Dytes) diet at 5 wks of age for 5 wks. Weights were recorded and stool collected. All mice then had 3% DSS replace their water, for 5 days. Mice were observed for diarrhea and occult blood. After the DSS, facility water was returned for 1 day prior to postmortem analyses. Mice were scanned using dual-energy X-ray absorptiometry (DEXA) for measures of fat, lean and fat mass, and bone density. Their colons were resected and fixed for histopathology. Stool was banked frozen until processed for sequencing using 16S Ribosomal primers. Results Three F2 litters were comprised of ratios of HZ:WT:SUCNR1-KO of 14:7:2. SUCNR1-KO mice (n=2 female) had a greater increase in weight compared to other genotypes during the obesity-induction phase. Weight loss during the DSS phase was similar across all genotypes. All mice had blood in their stool. DEXA measures did not differ between genotypes. All genotypes of mice had inflamed colons. Conclusions SUCNR1-KO mice are not resistant to obesity, nor from colitis when consuming the obese diet, outcomes that do not support our hypothesis. It remains to be determined whether the diet alters the microbiome resulting in SUCNR1-KO mice being suscueptible to colitis. Microbial sequencing is underway. Funding Agencies IWK Health Project Grant
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".