在菌株水平分析克罗恩病患者的黏膜相关菌群
创作:aluba 审核:aluba 06月08日
  • 收集5名克罗恩病患者的活检样本,进行厌氧菌群培养+宏基因组测序(MC-MGS);
  • 与直接提取活检样本中的DNA并进行16S rRNA测序相比,MC-MGS可完整地获得粘膜相关菌群的功能特征;
  • MC-MGS能够以菌株水平的分辨率分析肠杆菌科及其相关的毒力因子,并揭示了其脲酶活性可能促进了患者的肠道菌群失调;
  • 共恢复了47个高质量的宏基因组组装基因组(MAG),在5名患者中均恢复了高质量的大肠杆菌MAG。
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aluba
黏膜相关菌群被认为是克罗恩病的潜在驱动因素,但较低的菌群密度及人体DNA的干扰限制了对黏膜相关菌群的研究。ISME Journal上发表的一项最新研究,通过体外厌氧培养+宏基因组测序相结合的方式,对克罗恩病患者的黏膜相关菌群进行了菌株水平的深入分析,发现克罗恩病患者的粘膜相关菌群具有高度个体化的分类群及功能特征。
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ISME Journal [IF:10.302]

Novel strain-level resolution of Crohn's disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing

结合体外菌群培养与宏基因组测序,对克罗恩病中的粘膜相关菌群进行菌株水平分析

10.1038/s41396-021-00991-1

05-25, Article

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The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn's disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn's disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn's disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

First Authors:
J J Teh

Correspondence Authors:
M Morrison

All Authors:
J J Teh,E M Berendsen,E C Hoedt,S Kang,J Zhang,F Zhang,Q Liu,A L Hamilton,A Wilson-O'Brien,J Ching,J J Y Sung,J Yu,S C Ng,M A Kamm,M Morrison

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