Nature:肠菌可在宿主内演化出致病的移位能力
创作:mildbreeze 审核:mildbreeze 08月01日
  • 结合体内演化实验和比较基因组学分析,发现肠道致病共生菌鹑鸡肠球菌(Eg)可演化出多个谱系以适应小鼠的不同肠道微环境(肠腔vs黏膜);
  • 不同Eg菌株有不同的特征:与适应肠腔的菌株相比,适应肠黏膜的菌株能逃避宿主的免疫检测和清除,穿过肠屏障移位并存活于肠系膜淋巴结和肝脏,并引发肠道和肝脏炎症;
  • 这与菌株的特定调节基因突变、基因表达程序改变和胞壁结构重塑有关;
  • 在其他肠菌(如鼠李糖乳杆菌)中也有适应肠腔或黏膜的趋异演化现象,但移位能力与细菌种类有关。
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mildbreeze
随着时间的推移,我们肠道中定植的共生微生物也在不断地适应和演变。耶鲁大学Noah Palm团队在Nature发表的最新研究中提出一种假说,认为共生肠菌在宿主内的演化可能会影响其致病倾向。他们以一种致病共生菌——鹑鸡肠球菌为模型对这一假说进行了检验,该菌能在易感小鼠中移位至肝脏等组织器官,从而引发自身免疫病。通过分析小鼠粪便和肝脏中的分离菌发现,这种菌可在宿主内自发地发生趋异演化,产生适应肠腔或肠黏膜的不同谱系。其中,适应肠黏膜的菌株具有侵入性和致病特性特征,包括移位至肝脏、免疫逃逸和引发炎症;相比之下,适应肠腔的菌株则比较“良民”(且可能更具传播性)。总之,该研究在菌株水平和时间尺度上,为理解微生物相关疾病的发生发展提供了一个崭新的视角,在一定程度上可以解释菌群驱动的疾病中存在的“随机性”和年龄相关性。
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Nature [IF:69.504]

Within-host evolution of a gut pathobiont facilitates liver translocation

一种肠道致病共生菌的宿主内演化促进向肝脏移位

10.1038/s41586-022-04949-x

07-13, Article

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Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases1,2,3,4. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host5,6,7,8,9, raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared with ancestral and luminal E. gallinarum, mucosally adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and induce increased intestinal and hepatic inflammation. Mechanistically, these changes in bacterial behaviour are associated with non-synonymous mutations or insertion–deletions in defined regulatory genes in E. gallinarum, altered microbial gene expression programs and remodelled cell wall structures. Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.

First Authors:
Yi Yang

Correspondence Authors:
Noah W Palm

All Authors:
Yi Yang,Mytien Nguyen,Varnica Khetrapal,Nicole D Sonnert,Anjelica L Martin,Haiwei Chen,Martin A Kriegel,Noah W Palm

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