ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Phocaeicola coprophilus-Derived 6-Methyluracil Attenuates Radiation-Induced Intestinal Fibrosis by Suppressing the IDO1-Kynurenine-AHR Axis.
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.
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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.
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Who cites it
1 citing paper in PubMed.
- Multi-omics atlas of the bovine coronavirus-infected calf jejunum: reduction of Phocaeicola coprophilus and deoxycholic acid linked to Th17/Treg imbalance.NPJ biofilms and microbiomes · 2026Article
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Authors and funding
12 authors.
Funding
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.
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Registered trials
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.