Expression of MicroRNA‐148a and its Target Gene <i>EPAS1</i> (Endothelial PAS domain‐containing protein 1) in Intestinal Cells in Response to <i>Bifidobacterium bifidum</i> MIMBb75
Bibliographic record
Abstract
Bifidobacterium bifidum MIMBb75 is a probiotic strain isolated from healthy human feces. We have previously shown that this strain modulates the composition of the gut microbiota, a core probiotic benefit. Though, molecular mechanisms underlying effects specific to this strain are unknown, particularly at the transcriptional and post‐transcriptional (microRNA, miRNA) level. We found that the expression of intestinal miRNA, including miR‐148a, depends on the presence of the microbiota. MiR‐148a is a proposed biomarker of intestinal health. One of its target genes, EPAS1 , also called HIF2α (Hypoxia‐Inducible Factor 2α) is a pro‐inflammatory and pro‐carcinogenic transcription factor. The aim of this study was to investigate the effect of B. bifidum MIMBb75 on the intestinal expression of miR‐148a and EPAS1 in vitro and in vivo . The expression levels of miR‐148a and EPAS1 were assessed by qPCR using RNA extracted from Caco‐2 cells incubated with B. bifidum MIMBb75, B. bifidum NCC390 or B. longum NCC 2705 (cell ratio of 10:1) or control vehicle for 1, 4 and 24 hours at 37°C. To prove that EPAS1 gene expression changes do indeed depend on miR‐148a modulation by B. bifidum MIMBb75, miRNA silencing was performed via transfection of miR‐148a inhibitor in Caco‐2 cells for 72h, followed by incubation of transfected cells with B. bifidum MIMBb75. In addition, C57BL/6J male mice were gavaged for 2 or 14 days with 10 8 colony forming units of B. bifidum MIMBb75/day or vehicle alone and sacrificed by cervical dislocation. Caecum was used for RNA extraction and gene expression analysis as described above. Of the three strains tested, only B. bifidum MIMBb75 showed a significant upregulation of miR‐148a after 1 and 4 hours of co‐incubation with Caco‐2 cells (P <0.01), but not at 24h. Oral administration of B. bifidum MIMBb75 increased significantly miR‐148a expression in the caecum after 2 days (P< 0.05) but not after 14 days of probiotic administration, which was accompanied by a decrease of EPAS1 expression (P<0.01) at day 2. In vitro silencing of miR‐148a using miRNA inhibitor constructs reversed EPAS1 downregulation. This study brings a new concept of strain‐ and time‐dependent bifidobacteria‐host crosstalk via microRNA. Because early exposure to B. bifidum MIMBb75 repressed the expression of EPAS1 , this probiotic may be helpful in intestinal inflammatory conditions associated with EPAS1 over‐expression, such as colitis. Probiotic‐dependent regulation of host gene expression via miRNA may open the way to new therapeutic avenues. Support or Funding Information NSERC, JP Bickell Foundation, Lawson Family Chair in Microbiome Nutrition Research
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".