Attenuated fibrosis in specific pathogen‐free microbiota in experimental cholestasis‐ and toxin‐induced liver injury
Bibliographic record
Abstract
In advanced chronic liver disease (CLD), the translocation of intestinal bacteria and the resultant increase of proinflammatory cytokines in the splanchnic and systemic circulation may contribute to the progression of fibrosis. We therefore speculated that fibrosis and portal hypertension (PHT) would be attenuated in a mouse model of limited intestinal colonization with altered Schaedler flora (ASF) compared to a more complex colonization with specific pathogen‐free (SPF) flora. We induced liver fibrosis in ASF and SPF mice by common bile duct ligation (BDL) or by carbon tetrachloride (CCl 4 ) treatment. We then measured portal pressure (PP), portosystemic shunts (PSSs), and harvested tissues for further analyses. There were no differences in PP between sham‐treated ASF or SPF mice. After BDL or CCl 4 treatment, PP, PSSs, and hepatic collagen deposition increased in both groups. However, the increase in PP and the degree of fibrosis was significantly higher in ASF than SPF mice. Expression of fibrotic markers α‐smooth muscle actin, desmin, and platelet‐derived growth factor receptor β were significantly higher in ASF than SPF mice. This was associated with higher activation of hepatic immune cells (macrophages, neutrophils) and decreased expression of the intestinal epithelial tight junction proteins (claudin‐1, occludin‐1). In 2 models of advanced CLD, SPF mice presented significantly attenuated liver injury, fibrosis, and PHT compared to ASF mice. In contrast to our hypothesis, these findings suggest that a complex intestinal microbiota may play a “hepatoprotective” role.—Moghadamrad, S., Hassan, M., McCoy, K. D., Kirundi, J., Kellmann, P., De Gottardi, A. Attenuated fibrosis in specific pathogen‐free microbiota in experimental cholestasis‐ and toxin‐induced liver injury. FASEB J. 33, 12464–12476 (2019). www.fasebj.org
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".