Ablation of Intestinal Epithelial Sialylation Predisposes to Acute and Chronic Intestinal Inflammation in Mice
Bibliographic record
Abstract
Background & Aims Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis. Methods Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1 –/– mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1 –/– mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and mutiomics studies. Results IEC Slc35a1 –/– mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1 –/– mice had spontaneous tumors in the rectum greater than the age of 12 months. TM-IEC Slc35a1 –/– mice were highly susceptible to acute inflammation induced by 1% dextran sulfate sodium versus control animals. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1 –/– mice showed altered microbiota with an increase in Clostridium disporicum , which is associated a global reduction in the abundance of at least 10 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil led to more severe small intestine mucositis in the IEC Slc35a1 –/– mice versus wild-type littermates, which was associated with reduced Lgr5 + cell representation in small intestinal crypts in IEC Slc35a1 -/-;Lgr5-GFP mice. Conclusions Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.
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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".