小柯机器人

美国耶鲁大学医学院Noah W. Palm团队发现，肠道病原体在宿主体内的进化促进肝脏的转移。该项研究成果于2022年7月13日在线发表在《自然》杂志上。

研究人员发现，模型肠道致病菌Enterococcus gallinarum的宿主内进化促进了细菌的转移和炎症的发生。利用体内实验进化和比较基因组学的结合，研究人员发现E. gallinarum分化为独立的谱系，从而适应在肠道内的管腔或粘膜环境定居。与祖先和腔内E. gallinarum相比，适应粘膜的菌株可以逃避免疫系统的检测和清除，表现出更多的转移到肠系膜淋巴结和肝脏内并存活下来，并诱发更多的肠道和肝脏炎症。

从机制上讲，细菌行为的这些变化与胆碱酯酶的非同义突变或确定的调节基因的插入-删除、微生物基因表达程序的改变和细胞壁结构的重塑有关。在一个基于单克隆的宿主内进化模型中，雷特氏乳杆菌也表现出大致相似的分化进化模式和增强的免疫逃避。总的来说，这些研究将宿主内进化定义为共生体致病性的一个关键调节器，为微生物群驱动的疾病的发展和进展提供了一个独特的随机性来源。

据悉，有能力穿越肠道屏障的肠道共生细菌可以推动各种免疫介导的疾病的发展。然而，决定细菌易位的关键因素仍不清楚。最近的研究显示，肠道微生物群菌株可以在宿主的一生中不断适应和进化，这就提出了一种可能性，即个别共生细菌本身随时间的变化可能会影响它们引发炎症性疾病的倾向。

附：英文原文

Title: Within-host evolution of a gut pathobiont facilitates liver translocation

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

Issue&Volume: 2022-07-13

Abstract: 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.

DOI: 10.1038/s41586-022-04949-x

Source: https://www.nature.com/articles/s41586-022-04949-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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