Depletion of SCFA-fermenting gut bacteria alters the epigenome of hematopoietic stem and progenitor cells
Bibliographic record
Abstract
Abstract Gut dysbiosis alters the development and severity of atopic disease. We previously demonstrated that nursing dams and newborn mice treated with low-dose vancomycin alters gut microbial diversity with a marked loss of bacteria that produce short-chain fatty acids (including butyrate). Vancomycin-induced gut dysbiosis enhances the TH2 response to lung allergens due to altered dendritic cell trafficking and activation in addition to modifying the behavior of other mature leukocyte lineages. Butyrate supplementation reverses the vancomycin-induced TH2 pro-inflammatory phenotype. Butyrate is known to exert some of its effects on target cells by inhibiting histone deacetylases (HDACs) with consequent effects on gene expression. Consistent with a role for epigenetic skewing of the hematopoietic compartment, we found that engraftment of total bone marrow from dysbiotic mice transferred enhanced TH2 proclivity in normobiotic recipients. Strikingly, we found unique regulatory states (H3K27ac marks) in purified hematopoietic stem and progenitor cells (HSPC) of TH2-skewed recipient mice. Single cell RNA sequence analyses identified a distinct transcriptomic signature in HSPC of dysbiotic mice that was reversed by butyrate supplementation. Together, these data suggest that the gut microbiome alters gene expression in blood progenitor cells with long term consequences on the immune response to peripheral allergens.
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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 | 0.000 |
| 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".