Evidence map›Paper›PMID 42523540›Full record

ArticlebioRxiv : the preprint server for biology2026

Gut microbiome derived folate metabolite suppresses colorectal cancer progression.

Rebecca Danner, Juyeong Cho, Zachary Detwiler, Jonathan Williams, Jiyoung Amanda Han, Chang Yang, Xavier Diebold, Katerina Maeder, Jonathan G Van Vranken, Allison S Walker and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Rebecca DannerDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Juyeong ChoDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Zachary DetwilerWisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Jonathan WilliamsDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Jiyoung Amanda HanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Chang YangDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Xavier DieboldDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Katerina MaederDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Jonathan G Van VrankenDepartment of Cell Biology, Harvard Medical School, Cambridge, MA, 02115, USA.
Allison S WalkerDepartment of Chemistry, Vanderbilt University, Nashville, TN, 37240, USA.ORCID 0000-0001-5666-7232
Cammie LesserDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, Massachusetts 02111, USA.ORCID 0000-0002-1702-6333
Snehal N ChaudhariDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.ORCID 0000-0003-4389-3366

Funding

Biotechnology Training ProgramT32GM135066 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SCOTT M. COYLE, BRIAN G FOX · 2020 to 2026
$7.0M
Elucidating the role of the microbiome in inducing gut permeability and inflammationR00DK128503 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI Snehal N. Chaudhari · 2024 to 2026
$727k
NIDDK NIH HHS R00 DK128503NIGMS NIH HHS T32 GM135066
6 · The paper itself

Abstract

The gut microbiota influences colorectal cancer (CRC) progression, primarily through the secretion of small molecule metabolites. While numerous microbial products are known to drive CRC, endogenous protective mechanisms remain largely uncharacterized. Utilizing a folate metabolomics platform, we demonstrate that the healthy gut microbiota produces folinic acid (FA), a known chemotherapeutic adjuvant also known as leucovorin. This microbially derived folinic acid is progressively depleted in mouse models of colitis-associated CRC and in human clinical metagenomic cohorts with advancing disease severity. Mechanistically, folinic acid acts as a signaling molecule that directly binds and inhibits the intracellular protease calpain-2. This interaction stabilizes epithelial E-cadherin protein expression and suppresses CRC epithelial-to-mesenchymal transition driving metastasis. Genetically manipulating gut microbial production of FA is sufficient to modulate CRC

Identifiers

PMID42523540
PMCPMC13405309

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.