HIF-1 attenuates high-fiber diet-mediated proliferation and stemness of colonic epithelium
Bibliographic record
Abstract
The complex interplay between diet, microbiota, and host is exemplified by the effects of dietary fiber on the intestine. Inulin ingestion triggers epithelial changes in the colon that depend on microbiota-derived molecules, including enhanced proliferation, increased mucus production, and elevated antimicrobial peptide secretion. Here we employed a multilayered and multi-omics approach, including dietary interventions, intestinal organoids, and both genetic and pharmacological interventions to investigate the impact of inulin on two aspects of diet-microbiota-host interactions: intestinal hypoxia and hypoxia-inducible factor (HIF)-1 signaling in intestinal epithelial cells (IECs). We found that inulin, a soluble fiber, promotes intestinal hypoxia, stabilizing HIF-1 in IECs in a microbiota- and host-dependent manner. Furthermore, we show that HIF-1 stabilization modulates intestinal stem cell (ISC) function through metabolic reprogramming in a microbiota-dependent manner. Our findings reveal an unrecognized role for HIF-1 in orchestrating microbiota-dependent epithelial metabolism and proliferation in the colon, underscoring the complexity of diet-microbiota-host interactions.
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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".