Abstract 2239 The role of gut microbiota in modulating intestinal barrier integrity in vitamin D-supplemented C57BL/6 mice
Bibliographic record
Abstract
Vitamin D (VD) is an essential vitamin known for its role in maintaining bone health. In recent years, low VD has been shown to increase the risk for “leaky gut” and gastrointestinal (GI) diseases such as inflammatory bowel diseases and colorectal cancer. These observations are consistent with gut dysbiosis, leading us to a role gut microbiota in modulating colonic vitamin D signaling and its subsequent impact on intestinal permeability. This study aims to investigate the role of gut microbiota in promoting intestinal barrier integrity through the activation of colonic vitamin D signaling in mice. Male and female C57BL/6J mice at 6-week-old were randomized into 4 groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: 1) standard AIN-93G control diet (CTR), 2) CTR + antibiotics (AB), 3) CTR + 5000 IU vitamin D3 (VD), and 4) VD + antibiotics (VD + AB). Colon mucosa was collected at the end of the study for analysis of mRNA expressions. Activation of VD signaling in the colon was assessed by colonic expression of vitamin D receptor (VDR). Our data show that colonic VDR was 3-fold higher in the VD-fed mice compared to CTR mice (P = 0.04), though no changes in serum 1,25-dihydroxycholecalciferol, the active form of VD, was observed among all groups. Subsequently, expression of tight junction proteins (i.e. ZO-1, occludin, and claudin-1) assessed to examine the effect of VD on intestinal permeability in the presence of gut microbiota. Colonic expression of occludin 2-fold higher in VD mice compared to CTR mice (P = 0.025) and was not affected by AB treatment. In contrast, colonic ZO-1 mRNA expression was greater in VD-supplemented group in the presence of gut microbiota, particularly with male mice where the expression of ZO-1 was 6-fold greater compared to CTR (P = 0.004) and VD + AB (P = 0.023) male mice, respectively. Interestingly, a positive correlation was detected between colonic expression of VDR and ZO-1 (Pearson's correlation = 0.554; P < 0.001). No differences were detected with colonic claudin-1 mRNA expression. Overall, our study suggest a possible role of VDR in regulating intestinal permeability, a phenotype that could be dependent on gut microbiota. Because maintenance of intestinal barrier function is critical for GI inflammation, activation of colonic VD signaling via VD supplementation may serve as a strategy for prevention of GI diseases.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".