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Record W4415388123 · doi:10.1101/2025.10.20.683425

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

2025· preprint· en· W4415388123 on OpenAlexaff
Fenja Amrei Schuran, Neha Mishra, Víctor A. López-Agudelo, Nina Sommer, Alesia Walker, Finn Hinrichsen, Ting Gong, Félix Gilbert, Archana Bhardwaj, Sven Künzel, Saskia Weber‐Stiehl, Go Ito, Florian Tran, Mathieu Groussin, Christoph Roecken, Juan D. Matute, Stefan Schreiber, Josef Penninger, Richard S. Blumberg, Philippe Schmitt‐Kopplin, John F. Baines, Felix Sommer, Philip Rosenstiel

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNursing
TopicClinical Nutrition and Gastroenterology
Canadian institutionsUniversity of British Columbia
FundersNational Institutes of HealthBundesministerium für Bildung und ForschungDeutsche Forschungsgemeinschaft
KeywordsMalnutritionIntestinal epitheliumEpitheliumDNA methylationFunction (biology)Paneth cellTranscriptomeGenePhenotype

Abstract

fetched live from OpenAlex

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.021
GPT teacher head0.267
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicClinical Nutrition and Gastroenterology→French-language works237,207→