Gut Commensal Antibiotic-Resistant <i>Parabacteroides goldsteinii</i> Ameliorates Mouse Colitis through Valine–Isobutyrate Metabolism
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant Parabacteroides goldsteinii in a colitis mouse model. Our results further indicate that the gavage administration of P. goldsteinii AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in P. goldsteinii ΔilvE mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic–metabolite axis wherein P. goldsteinii facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota restoration in refractory UC management.
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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 | 0.001 | 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 it