基于测序的肠道菌群研究是检测结直肠癌（CRC）相关微生物的有价值方法，然而，这些研究往往受到肠道准备的影响。本研究评估了在没有术前肠道准备的情况下，通过对接受结肠切除手术的11例患者肿瘤和癌旁正常组织中的微生物群落进行厘米尺度分析，以确定与CRC相关的黏膜菌群的可行性。通过高通量16S rRNA基因测序发现，片段与非肿瘤微生物群落之间的差异在患者之间变化较大。对于一些患者，与结直肠癌发生机制有关的属类群和在CRC中作用不甚明确的属类群在肿瘤组织中富集，而对于其他患者，肿瘤和非肿瘤微生物群落非常相似。值得注意的是，肿瘤相关粘膜中属类群的富集非常局部，与肿瘤离得几厘米开外就不再明显。通过短期液体培养和宏基因组学，我们进一步获得了一百多个宏基因组组装的基因组，其中一些代表了在肿瘤样本中富集的细菌。这是第一批对未经干扰的肠粘膜菌群在未接受预处理的CRC患者的切除结肠组织样本中进行分析的研究之一。未来的大型队列研究有望阐明患者肿瘤部位菌群出现变异的原因和后果。版权所有© 2023 Fukuoka, Tourlousse, Ohashi, Suzuki, Nakagawa, Ozawa, Ishibe, Endo 和 Sekiguchi。

Sequencing-based interrogation of gut microbiota is a valuable approach for detecting microbes associated with colorectal cancer (CRC); however, such studies are often confounded by the effect of bowel preparation. In this study, we evaluated the viability of identifying CRC-associated mucosal bacteria through centimeter-scale profiling of the microbiota in tumors and adjacent noncancerous tissue from eleven patients who underwent colonic resection without preoperative bowel preparation. High-throughput 16S rRNA gene sequencing revealed that differences between on- and off-tumor microbiota varied considerably among patients. For some patients, phylotypes affiliated with genera previously implicated in colorectal carcinogenesis, as well as genera with less well-understood roles in CRC, were enriched in tumor tissue, whereas for other patients, on- and off-tumor microbiota were very similar. Notably, the enrichment of phylotypes in tumor-associated mucosa was highly localized and no longer apparent even a few centimeters away from the tumor. Through short-term liquid culturing and metagenomics, we further generated more than one-hundred metagenome-assembled genomes, several representing bacteria that were enriched in on-tumor samples. This is one of the first studies to analyze largely unperturbed mucosal microbiota in tissue samples from the resected colons of unprepped CRC patients. Future studies with larger cohorts are expected to clarify the causes and consequences of the observed variability in the emergence of tumor-localized microbiota among patients.Copyright © 2023 Fukuoka, Tourlousse, Ohashi, Suzuki, Nakagawa, Ozawa, Ishibe, Endo and Sekiguchi.