Mechanisms underlying bacteriophages and bacteria stable coexistence and its consequences on gut microbiome function.

噬菌体和细菌稳定共存的机制及其对肠道微生物组功能的影响。

• 批准号: 446067148
• 负责人: Professorin Dr. Barbara Stecher
• 金额: --
• 依托单位: Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/446067148?language=en
• 关键词: Mechanisms; underlying; bacteriophages; bacteria; stable

An increasing number of human diseases is associated with an altered intestinal microbiota (IM). The IM consists of trillions of microbes including viruses amongst which bacteriophages (phages) that predate on bacteria are the most abundant. Phages are important effectors and indicators of human health and disease by managing specific bacterial population structures and by interacting with the mucosal immune system. Despite metagenome-based studies have addressed their abundance, diversity and stability over time in the gut, little in known on the role of phages in IM homeostasis and its impact on global microbiome functions. Furthermore, there is a gap in knowledge pertaining to the mechanisms by which phages and their bacterial hosts dynamically interact over time.Humans harbor personalized viromes exhibiting high temporal stability. Virome composition of healthy individuals correlates with bacterial communities and is altered during inflammatory disease. Interestingly, phages can drive proinflammatory immune responses in the gut and aggravate colitis symptoms. A current limitation to our understanding of the role of phages in the IM is the lack of suitable model systems to probe phage functions and dissect the mechanisms of phage-bacteria interactions. To overcome this limitation, we employ a defined synthetic bacterial community, the Oligo-Mouse-Microbiota (OMM) and strain-specific phages in stably colonized gnotobiotic mice. In PhaStGut, we will conduct an in-depth characterization of phage ecology and study their influence on the microbiome and related functions in the gut. In addition, we will study the mechanisms underlying stable coexistence of phages and their host bacteria in the gut. The final goal is to refine strategies for phage-based IM engineering. Our highly interdisciplinary team, consisting of four partners, will use an integrated approach, combining meta-transcriptomics, meta-metabolomics and 3D DNA capture in gnotobiotic mice. Thereby, we will uncover mechanisms governing the dynamic interplay between phages and their host bacteria that shape the mammalian IM. PhaStGut will open avenues for the development of phage-guided strategies for microbiome engineering to sustain human health

越来越多的人类疾病与肠道微生物群（IM）的改变有关。IM由数万亿的微生物组成，包括病毒，其中噬菌体（噬菌体）是最丰富的细菌。噬菌体通过管理特定的细菌群体结构和与粘膜免疫系统相互作用，是人类健康和疾病的重要效应子和指示剂。尽管基于宏基因组的研究已经解决了它们在肠道中随时间推移的丰度、多样性和稳定性，但对它们在IM稳态中的作用及其对全球微生物组功能的影响知之甚少。此外，关于病毒和它们的细菌宿主随时间动态相互作用的机制的知识还存在空白。人类具有表现出高时间稳定性的个性化病毒组。健康个体的病毒组组成与细菌群落相关，并且在炎性疾病期间发生改变。有趣的是，结肠炎可以驱动肠道中的促炎免疫反应并加重结肠炎症状。目前我们对噬菌体在IM中的作用的理解的限制是缺乏合适的模型系统来探测噬菌体功能和剖析噬菌体-细菌相互作用的机制。为了克服这一局限性，我们采用了一个定义的合成细菌群落，寡小鼠微生物群（OMM）和菌株特异性大肠杆菌在稳定定殖的gnotobiotic小鼠。在PhaStGut中，我们将深入研究噬菌体生态学，并研究它们对肠道微生物组和相关功能的影响。此外，我们还将研究肠道中细菌及其宿主细菌稳定共存的机制。最终目标是完善基于噬菌体的IM工程的策略。我们的高度跨学科团队由四个合作伙伴组成，将使用综合方法，将元转录组学、元代谢组学和知菌小鼠的3D DNA捕获相结合。因此，我们将揭示的机制，管理动态之间的相互作用，细菌和宿主的形状哺乳动物IM。PhaStGut将为开发噬菌体指导的微生物组工程策略开辟道路，以维持人类健康