Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Cell Host Microbe. 2020 Apr 8;27(4):585-600.e4. doi: 10.1016/j.chom.2020.03.005. Epub 2020 Apr 1.
The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.
肠道微生物群与结直肠癌（CRC）有关，但 CRC 之前的因果变化尚未阐明。为了前瞻性评估结直肠肿瘤前的微生物组变化，我们使用粪便的 16S rRNA 基因测序、宏基因组和宏转录组测序，对 100 例林奇综合征患者的样本进行了研究。结肠切除术和 CRC 病史对微生物组图谱的影响最大。一组梭菌科在与基线腺瘤相对应的粪便中被消耗，而脱硫弧菌在粪便和黏膜活检中均被富集。利用粪便宏转录组学构建的分类器在预测结直肠腺瘤的间隔发展方面具有适度的能力。预测性转录本与鞭毛蛋白贡献者和氧化代谢微环境的变化相对应，这可能是局部 CRC 发病机制中的因素。这表明前瞻性微生物组监测腺瘤的效果可能有限，但支持这些在结直肠肿瘤中持续存在的早期微生物变化的潜在因果关系。
