与许多疾病一样，结直肠癌 (CRC) 的肿瘤形成是多因素的，涉及免疫、环境因素和导致疾病发展的各种遗传因素。越来越多的证据表明肠道微生物组与结直肠癌的发生和发展有关，并且这些微生物对于免疫成熟很重要。然而，缺乏将微生物谱、T 细胞受体 (TCR) 和人类 CRC 体细胞突变整合起来的系统视角。在这里，我们报告了 CRC 患者 (n = 107) 和健康供体 (n = 30) 外周血中表达的 TCRβ 库的独特特征。 CRC 患者的大 TCRβ 克隆数量增加，但 TCR 多样性非常低。宏基因组测序数据显示，与 HC 个体 (n = 30) 相比，CRC 患者 (n = 97) 中具核梭杆菌 (F. nucleatum)、大肠杆菌和 Dasheen 花叶病毒的相对丰度持续升高。与 HC (n = 30) 相比，CRC (n = 97) 中普拉梭菌和罗斯氏菌的丰度降低。研究了结直肠癌中靶基因（16个基因，n = 79）的体细胞突变与TCR克隆性和微生物生物标志物之间的相关性。重要的是，我们构建了一个基于微生物组和 TCR 库的随机森林分类器（包含 15 个特征），可用作筛查 CRC 患者的临床检测方法。我们还分析了具核梭菌特异性 TCR 库特征。总的来说，我们的大队列多组学数据旨在识别新的生物标志物，为结直肠癌检测和诊断的临床决策提供信息，这可能具有病因学和诊断意义。

As with many diseases, tumor formation in colorectal cancer (CRC) is multifactorial and involves immune, environmental factors and various genetics that contribute to disease development. Accumulating evidence suggests that the gut microbiome is linked to the occurrence and development of CRC, and these microorganisms are important for immune maturation. However, a systematic perspective integrating microbial profiling, T cell receptor (TCR) and somatic mutations in humans with CRC is lacking. Here, we report distinct features of the expressed TCRβ repertoires in the peripheral blood of and CRC patients (n = 107) and healthy donors (n = 30). CRC patients have elevated numbers of large TCRβ clones and they have very low TCR diversity. The metagenomic sequencing data showed that the relative abundance of Fusobacterium nucleatum (F. nucleatum), Escherichia coli and Dasheen mosaic virus were elevated consistently in CRC patients (n = 97) compared to HC individuals (n = 30). The abundance of Faecalibacterium prausnitzii and Roseburia intestinalis was reduced in CRC (n = 97) compared to HC (n = 30). The correlation between somatic mutations of target genes (16 genes, n = 79) and TCR clonality and microbial biomarkers in CRC had been investigated. Importantly, we constructed a random forest classifier (contains 15 features) based on microbiome and TCR repertoires, which can be used as a clinical detection method to screen patients for CRC. We also analysis of F. nucleatum-specific TCR repertoire characteristics. Collectively, our large-cohort multi-omics data aimed to identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC, which is of possible etiological and diagnostic significance.