Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis
This paper has a computational component, but its primary data is legally or ethically access-restricted — identifiable patient cohorts, rare-disease genomes, or controlled-access biobanks that cannot be openly shared. The reproduction therefore could not be attempted. That is a neutral verdict: it does not mean the result is wrong or that the authors fell short — only that, for legitimate privacy reasons, it cannot be independently checked from public data. We deliberately do NOT assign a 0–100 score here, because a low number would wrongly read as a failed reproduction.
▸Reproduction agent’s raw note
DROP (data_unavailable). The only pipeline-derived results in this 2017 Nature Medicine paper (Worthmann et al., nm.4357) are the IKMB-Kiel 16S gut-microbiome analyses of mouse feces: weighted-UniFrac beta-diversity MDS (Suppl Fig 1a), mvabund significantly-altered-OTU heatmap (1b), family/genus relative abundance (1c,d), and alpha diversity + pairwise Wilcoxon (1e). The raw 16S sequencing data was never deposited in any discoverable public repository and no derived count/abundance matrix is shipped; the Online Methods are paywalled. Exhaustively re-verified across NCBI (elink bioproject/sra/gds), ENA (Xref REST + portal title search), EuropePMC (core dbCrossReferences=N), the CRC1182 metaorganism portal, and figshare/github web search -- all negative. As published, the paper's computational results are NOT reproducible from public data. All wet-lab/analytical-chemistry results (bile acids, plasma lipids, BAT/thermogenesis, calorimetry, qPCR, histology, cholesterol balance) are out of scope (non-pipeline). NOTE: the room operator is a co-author (Schlein C); a co-author-supplied copy of the raw 16S fastqs + the Franke-lab pipeline would upgrade this from drop to an attempted reproduction -- requested in-room. Absent that, this is the final, well-founded public-reproducibility verdict.
These records describe the outcome of reproduction attempts carried out autonomously by brainbox using large language models (LLMs). They are not peer review, not an audit, and not a determination of error or misconduct by any author. A verdict reflects what one attempt could or could not reproduce — which may depend on data access, undocumented parameters, the computing environment, or the depth of effort — and not a judgement of the people who did the work. We can be wrong, and we correct mistakes quickly: every record carries a “report an error” button.
Assessment versions
Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.
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v1 current initial assessmentassessed: 2026-06-19 ⛓ 1118aa50d3ae
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Provenance — full disclosure
When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-22
- Rubric version
- not recorded
- Assessed by
- —
- Last updated
- 2026-07-31
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Scope — pmid-28604703
Paper: Worthmann A, John C, Rühlemann MC, et al. "Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis." Nature Medicine 23(7):839-849 (2017). DOI 10.1038/nm.4357. PMCID: none (paywalled, no open full text). Co-author: Schlein C (= room operator).
In-scope (pipeline-derived / bioinformatic)
The ONLY computational-pipeline results in this paper are the 16S rDNA gut microbiome analyses of mouse feces. Microbiome analysis was performed by M.C. Rühlemann, F.-A. Heinsen and A. Franke (Kiel IKMB). Pipeline elements named in the paper:
- 16S rDNA amplicon sequencing of feces.
- Beta diversity: weighted UniFrac distance → MDS/PCoA ordination (Supp Fig 1a: MDS1 53%, MDS2 27%).
- Significantly altered OTUs via mvabund (Wang et al. 2012, model-based multivariate abundance analysis) → hierarchical clustering heatmap (Supp Fig 1b).
- Alpha diversity (Observed OTUs/Genera, Shannon) with pairwise Wilcoxon Rank Sum Tests (Supp Fig 1e).
- Mean relative abundance at family/genus level (Supp Fig 1c,d).
These microbiome panels recur across several sub-experiments (chow WT warm n=8 / cold n=7; db/db; ezetimibe EZ warm n=10/cold n=9; cholestyramine Chol warm n=8/ cold n=8; an EZ 22°C arm warm n=6/cold n=8).
Out-of-scope (wet-lab / manual / analytical chemistry — NOT attempted)
- Plasma/fecal bile acid quantification (LC-MS/enzymatic).
- Plasma cholesterol, triglycerides, lipoprotein processing, BAT activation, thermogenesis / heat production, indirect calorimetry.
- qPCR (Cyp7b1 etc.), histology, food intake, feces production, cholesterol balance (Supplementary Table 1a/b — all wet-lab measurements).
- Genetic/pharmacological mouse interventions.
Reproducibility surface — BLOCKER
- Raw 16S data: NO public accession. Checked NCBI elink PMID→BioProject / SRA / GEO (all empty), ENA portal/title search (no match), Europe PMC datalinks (only Altmetric + MGI, no sequence DB). The paper carries no visible Data-availability/accession statement in the openly reachable HTML.
- No machine-readable abundance table in Supplementary Information (the single Supp Table 1 is wet-lab physiology; the SI is figures + that one table).
- Full Online Methods paywalled — exact pipeline (read processing, OTU picking, reference DB, rarefaction depth) not openly recoverable.
⇒ The in-scope pipeline results cannot be reproduced from public data as-is. Decision pending operator (co-author): can the raw 16S fastqs + exact bioinformatics pipeline be provided? Otherwise → drop (data_unavailable / no_data_accession). See ROOM_RESULT.json.
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
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Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.