Background/Objectives: Colorectal cancer (CRC) exhibits significant molecular heterogeneity, as reflected in Consensus Molecular Subtype (CMS) classification, and demonstrates extensive crosstalk with the microbiome. However, the role of the microbiome in determining subtypes of CRC, and CMS4 in particular, which represents an aggressive, stromal-rich variant associated with poor prognosis, remains poorly understood. Here, we reveal the role of the tumor microbiome in shaping the tumor microenvironment (TME) and its impact on CMS4 determination.Methods: A total of 25 CRC tissues were analyzed using RNA sequencing and classified with CMScaller to identify significantly enriched microbial species. Functional studies were performed using these CMS-specific microbial species and CMS2 organoids co-cultured with stromal (18Co) and immune (THP-1) cells.Results: 16S rRNA profiling of matched CRC tissues showed thatBacteroides fragiliswas significantly enriched in CMS4 tumors (linear discriminant analysis score = 4.7). Functional studies revealed that exposure to enterotoxigenicBacteroides fragilis(ETBF) induced CMS4-like features, including enhanced growth and gene expression patterns resembling those of primary CMS4 tumors.Conclusions: These findings suggest that ETBF contributes to the development of CMS4 and may facilitate the acquisition of aggressive phenotype associated with this CRC subtype.
**背景/目的：** 结直肠癌（CRC）表现出显著的分子异质性，这体现在共识分子分型（CMS）分类中，并且与微生物组存在广泛的相互作用。然而，微生物组在决定CRC亚型，特别是与不良预后相关的侵袭性、富含间质的CMS4亚型中的作用，目前仍知之甚少。本研究揭示了肿瘤微生物组在塑造肿瘤微环境（TME）中的作用及其对CMS4分型的影响。 **方法：** 本研究对25例CRC组织进行了RNA测序分析，并使用CMScaller进行分类，以鉴定显著富集的微生物物种。利用这些CMS特异性微生物物种，与基质细胞（18Co）和免疫细胞（THP-1）共培养的CMS2类器官进行了功能研究。 **结果：** 对匹配的CRC组织进行16S rRNA分析显示，脆弱拟杆菌在CMS4肿瘤中显著富集（线性判别分析得分 = 4.7）。功能研究表明，暴露于产肠毒素脆弱拟杆菌（ETBF）会诱导产生类似CMS4的特征，包括增强的生长以及类似于原发性CMS4肿瘤的基因表达模式。 **结论：** 这些发现表明，ETBF促进了CMS4亚型的形成，并可能有助于获得与该CRC亚型相关的侵袭性表型。
Bacteroides fragilisPromotes Mesenchymal Subtype in Colorectal Cancer
肿瘤(癌症)患者之家