Critical cross feeding mechanisms of microbial communities in the gut: menaquinone production and bacterial bioenergetics

肠道微生物群落的关键交叉喂养机制：甲萘醌生产和细菌生物能学

• 批准号: RGPIN-2022-04912
• 负责人: Burton, Jeremy
• 金额: $ 2.18万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761019
• 关键词: Critical; cross; feeding; mechanisms; microbial

Microbes interdepend on community members that are close in proximity for nutrients and other molecules. Highlighting the importance of certain metabolic by-products from bacterial community associates, a recent discovery from our group showed that acetate delivered to the colon could heavily promote keystone bacterial symbionts. Acetate is a short chain fatty acid which is usually rapidly taken in by the host and is not present in the colon in significant amounts. Its presence in the colon is typically only as a by-product of bacterial fermentation in small amounts. Akkermansia muciniphila is particularly stimulated by acetate which concurrently increased the microbial biosynthesis of menaquinone (MK; vitamin K2) with other bacterial members. MK is an important vitamin for both mammals and also bacteria in the process of energy generation. There is a paucity of information on the unique components that commensal bacteria for energy generation. Our new data suggests that bacteria in a broader community context may not be as selfish as they are traditionally perceived. We hypothesise that community sharing of molecules involved in energy generation, such as MK is a critical factor regulating the dynamic evolution of gut microbial communities. Here, we aim to better understand the major mechanistic interplay within the gut microbiota by this respiratory molecule. Our first objective encompasses using a gut model where we will screen for different acetate types which promote A. muciniphila and then monitor how altered MK biosynthesis impacts the system. We will collect a bacterial library for further analysis and examine the type of MK variant produced. The second objective will decipher the impact and transference of different bacterial MK types in pure and mixed bacterial cultures. These studies will help to bridge the knowledge gap to improve our understanding of human gut-associated microbial communities by characterizing the underlying energy-generating networks which support the co-existing of host-adapted species. Moreover, the findings will be applicable to broad aspects of microbial ecology, health and the food industry.

微生物相互依赖于离得很近的群落成员来获取营养和其他分子。强调细菌群落相关代谢副产物的重要性，我们小组最近的一项发现表明，输送到结肠的醋酸盐可以极大地促进关键细菌共生体。醋酸酯是一种短链脂肪酸，通常被宿主迅速吸收，在结肠中不会大量存在。它在结肠中的存在通常只是少量细菌发酵的副产物。嗜粘阿克曼氏菌特别受到醋酸盐的刺激，醋酸盐同时增加了微生物与其他细菌成员甲基萘醌（MK；维生素K2）的生物合成。MK是哺乳动物和细菌在能量生成过程中的重要维生素。关于共生细菌产生能量的独特成分的信息很少。我们的新数据表明，在更广泛的社区背景下，细菌可能不像传统上认为的那样自私。我们假设参与能量产生的分子（如MK）的群落共享是调节肠道微生物群落动态进化的关键因素。在这里，我们的目标是更好地了解这种呼吸分子在肠道微生物群中的主要机制相互作用。我们的第一个目标包括使用肠道模型，我们将筛选促进嗜粘杆菌的不同醋酸类型，然后监测改变的MK生物合成如何影响系统。我们将收集细菌文库进行进一步分析，并检查产生的MK变体的类型。第二个目标将破译不同细菌MK类型在纯和混合细菌培养中的影响和转移。这些研究将有助于弥合知识差距，通过表征支持宿主适应物种共存的潜在能量产生网络，提高我们对人类肠道相关微生物群落的理解。此外，研究结果将适用于微生物生态学，健康和食品工业的广泛方面。