哥伦比亚大学Harris H. Wang小组取得一项新突破。他们的最新研究探明了粪便脱叶测序捕获健康和炎症肠道的免疫动力学。这一研究成果发表在2025年11月17日出版的国际学术期刊《自然—生物技术》上。

在这里，研究团队引入了脱叶测序（Foli-seq）来分析来自上下胃肠道区域的粪便脱落真核信使RNA (feRNAs)，并表明这种“粪便脱叶”含有反映肠道和免疫功能的稳定RNA。通过选择性扩增目标转录本，Foli-seq展示了feRNAs的快速、准确、敏感和定量测量。在小鼠结肠炎模型中，feRNA揭示了不同类型肠道炎症特异性的上皮损伤、免疫反应和肠道恢复的时间过程。同时，他们的表皮和微生物组分析揭示了一个密集的宿主-微生物相互作用网络。

此外，该研究团队证明了炎症性肠病患者分层成与疾病严重程度相关的亚组。粪便Foli-seq是一种纵向研究肠道和描述其健康状况的无创策略。

据介绍，宏基因组测序和粪便代谢组学揭示了肠道微生物组对健康和疾病的影响。除了微生物群，粪便还含有脱落或脱落的宿主上皮细胞、分泌细胞和免疫细胞，但由于降解和交叉污染，这些细胞的RNA谱分析具有挑战性。

附：英文原文

Title: Fecal exfoliome sequencing captures immune dynamics of the healthy and inflamed gut

Author: Huang, Yiming, Sun, Yiwei, Ronda, Carlotta, Mavros, Chrystal F., Li, Jing, Jacobse, Justin, Huang, Lei H., Resnick, Samuel J., Giddins, Marla, Freedberg, Daniel E., Chavez, Alejandro, Goettel, Jeremy A., Wang, Harris H.

Issue&Volume: 2025-11-17

Abstract: Metagenomic sequencing and metabolomics of fecal matter have revealed the impact of the gut microbiome on health and disease. In addition to microbiota, feces also contain shed or exfoliated host epithelial, secretory and immune cells, but RNA profiling of these cells is challenging owing to degradation and cross-contamination. Here we introduce exfoliome sequencing (Foli-seq) to profile fecal exfoliated eukaryotic messenger RNAs (feRNAs) originating from the upper and lower gastrointestinal regions and show that this ‘fecal exfoliome’ harbors stable RNAs that reflect intestinal and immune function. By selectively amplifying targeted transcripts, Foli-seq demonstrates robust, accurate, sensitive and quantitative measurement of feRNAs. In murine colitis models, feRNA reveals temporal processes of epithelial damage, immune response and intestinal recovery specific to different types of gut inflammation. Simultaneous exfoliome and microbiome profiling uncovers a dense host–microbe interaction network. Moreover, we demonstrate stratification of patients with inflammatory bowel disease into subgroups that correlate with disease severity. Fecal Foli-seq is a noninvasive strategy to longitudinally study the gut and profile its health.

DOI: 10.1038/s41587-025-02894-4

Source: https://www.nature.com/articles/s41587-025-02894-4