小柯机器人

美国加州理工学院Rustem F. Ismagilov团队近期取得重要工作进展，他们研究开发了微生物富集方法，这一策略能够从富含宿主的样品中进行高通量宏基因组表征。相关研究成果2023年10月12日在线发表于《自然—方法学》杂志上。

据介绍，宿主和微生物相互作用已经通过微生物分类分析与健康和疾病状态联系起来，主要是通过16S核糖体RNA基因测序。然而，许多机制的见解仍还不清楚，部分原因是研究与哺乳动物组织相关微生物的基因组很困难，因为这些样本中宿主与微生物DNA的比例很高。

研究人员描述了一种微生物富集方法（MEM），他们在广泛的样本类型上进行了验证，包括唾液、粪便、肠道刮片和肠粘膜活检。MEM通过在微生物群落变化最小的情况下将宿主DNA减少1000倍以上，实现了对人类肠道活检微生物宏基因组的高通量表征（大约90%的分类群在MEM处理和未处理的对照组之间没有显著差异）。MEM处理的人类肠道活检的Shotgun测序能够表征沿胃肠道纵向的高丰度和低丰度微生物分类群、途径和基因。研究人员报道了直接从人类肠道活检中构建宏基因组组装的细菌和古菌基因组，其相对丰度低至1%。

总之，对宏基因组组装基因组的分析揭示了一些分类群小肠和大肠之间不同的亚群结构。MEM通过深入表征宿主组织相关微生物群落，为微生物组领域深入了解宿主-微生物相互作用开辟了新方法。

附：英文原文

Title: Microbial-enrichment method enables high-throughput metagenomic characterization from host-rich samples

Author: Wu-Woods, Natalie J., Barlow, Jacob T., Trigodet, Florian, Shaw, Dustin G., Romano, Anna E., Jabri, Bana, Eren, A. Murat, Ismagilov, Rustem F.

Issue&Volume: 2023-10-12

Abstract: Host–microbe interactions have been linked to health and disease states through the use of microbial taxonomic profiling, mostly via 16S ribosomal RNA gene sequencing. However, many mechanistic insights remain elusive, in part because studying the genomes of microbes associated with mammalian tissue is difficult due to the high ratio of host to microbial DNA in such samples. Here we describe a microbial-enrichment method (MEM), which we demonstrate on a wide range of sample types, including saliva, stool, intestinal scrapings, and intestinal mucosal biopsies. MEM enabled high-throughput characterization of microbial metagenomes from human intestinal biopsies by reducing host DNA more than 1,000-fold with minimal microbial community changes (roughly 90% of taxa had no significant differences between MEM-treated and untreated control groups). Shotgun sequencing of MEM-treated human intestinal biopsies enabled characterization of both high- and low-abundance microbial taxa, pathways and genes longitudinally along the gastrointestinal tract. We report the construction of metagenome-assembled genomes directly from human intestinal biopsies for bacteria and archaea at relative abundances as low as 1%. Analysis of metagenome-assembled genomes reveals distinct subpopulation structures between the small and large intestine for some taxa. MEM opens a path for the microbiome field to acquire deeper insights into host–microbe interactions by enabling in-depth characterization of host-tissue-associated microbial communities.

DOI: 10.1038/s41592-023-02025-4

Source: https://www.nature.com/articles/s41592-023-02025-4

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex