Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma

Abstract The intratumoral microbiota, fatty acid metabolism (FAM), and tumor microenvironment (TME) all provide insights into the management of colon adenocarcinoma (COAD). But the biological link among the three remains unclear. Here, we analyzed intratumoral microbiome samples and matched host tra...

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Main Authors: Guangyi Liu, Kun Liu, Lei Ji, Yang Li
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-87194-2
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author Guangyi Liu
Kun Liu
Lei Ji
Yang Li
author_facet Guangyi Liu
Kun Liu
Lei Ji
Yang Li
author_sort Guangyi Liu
collection DOAJ
description Abstract The intratumoral microbiota, fatty acid metabolism (FAM), and tumor microenvironment (TME) all provide insights into the management of colon adenocarcinoma (COAD). But the biological link among the three remains unclear. Here, we analyzed intratumoral microbiome samples and matched host transcriptome samples from 420 patients with COAD in The Cancer Genome Atlas (TCGA). All patients were divided into two subtypes (FAM_high and FAM_low) based on the Gene set variation analysis (GSVA) score of FAM pathway. Furthermore, we found significant difference in the intratumoral microbiota signatures between the two subtypes. In-depth analysis suggested that specific microbes in tumors may indirectly modify the TME, particularly stromal cell populations, by modulating the FAM process. More importantly, the crosstalk between the three can have a significant impact on prognosis, response to immunotherapy, and drug sensitivity of patients. Pathological image profiling showed that changes in the TME originating from intratumoral microbiota disturbance could be reflected in pathological image features. In summary, our study provides novel insights into the biological links among the intratumoral microbiota, FAM, and the TME in COAD, and offer guidance for the therapeutic opportunities that target intratumoral microbes.
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spelling doaj-art-234202c4651a45319a7c27d9d3b286be2025-01-26T12:29:49ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-87194-2Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinomaGuangyi Liu0Kun Liu1Lei Ji2Yang Li3Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityGeneis Beijing Co., Ltd.Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract The intratumoral microbiota, fatty acid metabolism (FAM), and tumor microenvironment (TME) all provide insights into the management of colon adenocarcinoma (COAD). But the biological link among the three remains unclear. Here, we analyzed intratumoral microbiome samples and matched host transcriptome samples from 420 patients with COAD in The Cancer Genome Atlas (TCGA). All patients were divided into two subtypes (FAM_high and FAM_low) based on the Gene set variation analysis (GSVA) score of FAM pathway. Furthermore, we found significant difference in the intratumoral microbiota signatures between the two subtypes. In-depth analysis suggested that specific microbes in tumors may indirectly modify the TME, particularly stromal cell populations, by modulating the FAM process. More importantly, the crosstalk between the three can have a significant impact on prognosis, response to immunotherapy, and drug sensitivity of patients. Pathological image profiling showed that changes in the TME originating from intratumoral microbiota disturbance could be reflected in pathological image features. In summary, our study provides novel insights into the biological links among the intratumoral microbiota, FAM, and the TME in COAD, and offer guidance for the therapeutic opportunities that target intratumoral microbes.https://doi.org/10.1038/s41598-025-87194-2Colon adenocarcinomaIntratumoral microbiotaFatty acid metabolismTumor microenvironment
spellingShingle Guangyi Liu
Kun Liu
Lei Ji
Yang Li
Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
Scientific Reports
Colon adenocarcinoma
Intratumoral microbiota
Fatty acid metabolism
Tumor microenvironment
title Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
title_full Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
title_fullStr Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
title_full_unstemmed Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
title_short Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
title_sort intratumoral microbiota fatty acid metabolism and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma
topic Colon adenocarcinoma
Intratumoral microbiota
Fatty acid metabolism
Tumor microenvironment
url https://doi.org/10.1038/s41598-025-87194-2
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AT leiji intratumoralmicrobiotafattyacidmetabolismandtumormicroenvironmentconstituteanunresolvedtrinityincolonadenocarcinoma
AT yangli intratumoralmicrobiotafattyacidmetabolismandtumormicroenvironmentconstituteanunresolvedtrinityincolonadenocarcinoma