Evidence map›Paper›PMID 41560360›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Phocaeicola coprophilus-Derived 6-Methyluracil Attenuates Radiation-Induced Intestinal Fibrosis by Suppressing the IDO1-Kynurenine-AHR Axis.

Jiaxin Zhang, Zhen Wang, Shuang Li, Chao Luo, Han Li, Shengjie Ma, Pai Wang, Heshi Liu, Lijun Sun, Yue Yin and 2 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Jiaxin ZhangDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Zhen WangDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Shuang LiDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Chao LuoDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
Han LiDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
Shengjie MaDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Pai WangDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Heshi LiuDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Lijun SunDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
Yue YinDepartment of Pharmacology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
Weizhen ZhangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, P. R. China.
Quan WangDepartment of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.ORCID https://orcid.org/0000-0001-6727-1508

Funding

Beijing Nova Program 20240484505Department of Science and Technology of Jilin Province YDZJ202402012CXJDDoctor of Excellence Program (DEP), The First Hospital of Jilin University JDYY-DEP-2022006National Natural Science Foundation of China 82270610National Natural Science Foundation of China 82330017Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0530100Youth Development Fund of the First Hospital of Jilin University JDYY15202429
6 · The paper itself

Abstract

Therapeutic options for radiation-induced intestinal fibrosis (RIF) remain limited. This study reveals that intestinal kynurenine (Kyn) is persistently elevated after radiation and correlates with fibrosis severity in both murine models and human rectal cancer samples. Exogenous Kyn exacerbated RIF, whereas inhibition of indoleamine 2,3-dioxygenase 1 (IDO1) attenuated fibrotic progression. Mechanistically, Kyn activates the aryl hydrocarbon receptor (AHR) to promote fibroblast activation and fibrosis. Antibiotic depletion of gut microbiota abrogates radiation-induced IDO1-Kyn upregulation and protects against RIF. Conversely, fecal microbiota transplantation from irradiated mice recapitulates the elevated IDO1-Kyn phenotype. Metagenomic analysis identify radiation-induced depletion of Phocaeicola coprophilus (P. coprophilus), whose abundance inversely correlates with Kyn levels. Supplementation with live P. coprophilus suppresses IDO1-Kyn signaling and ameliorates RIF. Untargeted metabolomics further show that radiation reduces 6-methyluracil, a metabolite derived from P. coprophilus. Exogenous 6-methyluracil replenishment inhibits repression of the IDO1-Kyn axis and mitigates fibrosis. Together, these findings define a microbiota-metabolite-host pathway in which radiation depletes P. coprophilus, leading to loss of 6-methyluracil and derepression of the IDO1-Kyn-AHR axis, thereby driving fibrogenesis. Restoration of either P. coprophilus or its metabolite 6-methyluracil represents a promising therapeutic strategy against RIF.

Indexed as

FibrosisIndoleamine-Pyrrole 2,3,-DioxygenaseIntestinesKynurenineReceptors, Aryl HydrocarbonUracilAnimalsGastrointestinal MicrobiomeHumansMiceMice, Inbred C57BLSignal TransductionIDO1 protein, mouseIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineReceptors, Aryl HydrocarbonUracilgut microbiotaIDO1kynurenine pathwayradiation‐induced intestinal fibrosis

Identifiers

PMID41560360
PMCPMC13042846

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.