{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:12Z","timestamp":1790575032226,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Intratumoral microbiota are emerging as important ecological components of the colorectal cancer (CRC) microenvironment. However, their stage\u2013associated patterns and coordination with host gene expression remain poorly understood. This study aimed to characterize stage\u2013associated associations between intratumoral microbiota and the host transcriptome in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We profiled 73 regional tumor specimens from 30 independent, treatment-na\u00efve CRC patients using full-length 16S rRNA gene sequencing and mRNA sequencing. Microbial diversity, predicted functional profiles, co-occurrence networks, differential abundance, and microbiota\u2013host transcriptome associations were analyzed. Regularized canonical correlation analysis and machine-learning modeling with SHAP-based feature interpretation were performed to identify stage-discriminative features. Candidate associations were evaluated in two independent public microbiome datasets. Mendelian randomization and immune-infiltration analyses were further conducted to explore the potential biological relevance of representative microbiota\u2013gene associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Disease stage was a major factor shaping intratumoral microbial composition. Advanced-stage CRC exhibited increased microbial \u03b1-diversity, distinct predicted functional profiles, and altered microbial co-occurrence patterns. Integrated microbiota\u2013transcriptome analysis identified ten genus-level and six species-level candidate microbiota\u2013gene association pairs. Core genera showed reproducible stage-discriminative signals in two independent public microbiome datasets. SHAP analysis identified the principal microbial and host transcriptomic features contributing to stage classification. Integrating microbial and host gene signatures improved classification performance, with the combined model achieving an AUROC greater than 0.90. The\n                      <jats:italic>Alloprevotella<\/jats:italic>\n                      \u2013MDH1 pair was selected as a representative association axis.\n                      <jats:italic>Alloprevotella<\/jats:italic>\n                      abundance was negatively correlated with MDH1 expression, while low MDH1 expression was associated with poorer survival and distinct metabolic\u2013immune states in CRC. Exploratory Mendelian randomization analysis provided preliminary genetic epidemiological support for an association between\n                      <jats:italic>Alloprevotella<\/jats:italic>\n                      abundance and CRC risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Intratumoral microbiota and host transcriptional profiles exhibit coordinated, stage-associated alterations in CRC. The identified microbiota\u2013gene associations, particularly the\n                      <jats:italic>Alloprevotella<\/jats:italic>\n                      \u2013MDH1 axis, provide potential biological links between tumor microbial ecology, host metabolism, immune states, and CRC progression. These findings support the value of integrated microbiome\u2013transcriptome analysis for characterizing the intratumoral microenvironment and identifying candidate microbial\u2013host regulatory relationships.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1934580","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:19Z","timestamp":1790574259000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intratumoral microbiota-host gene associations characterize stage-associated microecological patterns in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiyuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cao","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Yang","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, Fujian, China"]},{"name":"Department of Gastroenterology, Zhongshan Hospital of Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8971","DOI":"10.1038\/ncomms9971","article-title":"Systematic pan-cancer analysis of tumour purity","volume":"6","author":"Aran","year":"2015","journal-title":"Nat. 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