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.

中文翻译：

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林奇综合征粘膜和凳子微生物组的结构。

肠道菌群与大肠癌（CRC）有关，但尚未阐明CRC之前的因果关系。为了前瞻性地评估大肠肿瘤形成之前的微生物组变化，我们使用结肠活检的16S rRNA基因测序以及粪便的宏基因组和超转录组测序研究了来自100位Lynch综合征患者的样本。结肠切除术和CRC史代表了对微生物组谱的最大影响。粪便中有一部分梭菌科的枯竭菌，与基线腺瘤相对应，而粪中和黏膜活检组织中都富含脱硫弧菌。利用粪便转录组的分类器可适度地预测肿瘤前结肠腺瘤的间隔发展。预测的成绩单对应于鞭毛蛋白贡献者和氧化代谢微环境的转变，这可能是局部CRC发病机制的潜在因素。这表明前瞻性微生物组监测腺瘤的有效性可能有限，但支持了结肠瘤形成中这些一致的早期微生物变化的潜在因果关系。