Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species
Why this work is in the frame
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Bibliographic record
Abstract
Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota. Once absorbed, uroA can trigger mitophagy and aryl hydrocarbon receptor signaling pathways, altering host immune function, mitochondrial health, and intestinal barrier integrity. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing precursor (uroC) are unknown. Here, we use a combination of untargeted bacterial transcriptomics, proteomics, and comparative genomics to uncover an inducible uroC dehydroxylase (ucd) operon in Enterocloster species. We show that the ucd operon encodes a predicted molybdopterin-dependent enzyme complex that dehydroxylates urolithins at a specific position (9-OH). By interrogating publicly available metagenomics datasets, we observed that uroC-metabolizing Enterocloster species and ucd operon genes are prevalent in human feces. In ex vivo experiments with human fecal samples, only samples actively transcribing ucd could produce uroA, possibly explaining differences in urolithin metabolism between individuals. Collectively, this work identifies Enterocloster species and the ucd operon as important contributors to uroA production and establishes a multi-omics framework to further our mechanistic understanding of polyphenol metabolism by the human gut microbiota.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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