Host-microbe interactions: Harnessing co-evolution to treat disease

宿主-微生物相互作用：利用共同进化来治疗疾病

• 批准号: 10453473
• 负责人: Janelle S Ayres
• 金额: $ 134.68万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453473
• 关键词: Affect; Animal Model; Back; Communicable Diseases; Communication; Complex; Disease; Evolution; Functional disorder; Health; Health Promotion; Infection; Longevity; Methods; Microbe; Occupations; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Physiological; Physiology; Process; Property; Scientist; System; Techniques; Work; base; biological research; gut microbiota; healthspan; host-microbe interactions; microbiota; novel; novel strategies; novel therapeutic intervention; public health relevance; response

Abstract A new perspective for treating disease. There is a disconnect between our methods for treating diseases and our understanding of the mechanisms that keep us healthy; this needs to change. The past fifty years of biological research have done an excellent job of understanding disease pathogenesis by reducing the organism to its component parts, in order to understand the intricate details of how dysfunction of these parts leads to disease. A significant limitation to this approach, however, is that physiologies do not exist in isolation; when one system becomes dysfunctional, the whole body is affected. A second issue that complicates this approach is that current methods for treating disease primarily involve blocking pathogenic responses rather than inducing pathways that work to maintain health. The reason for this is two-fold: 1) scientists study disease, not health, and therefore do not understand the mechanisms that promote health; and 2) It is commonly assumed that blocking a pathogenic response will bring the patient back to a healthy state, which is not necessarily true. Therefore, rather than asking how we should treat disease, the question that should be asked is, “How is health maintained?” To understand and ultimately manipulate the complex multi-directional interactions that occur between all of our physiologies, a novel approach is proposed in this application. This approach is based on understanding that the body and its resident microbiota have co-evolved to rely on communication between all physiologies in order to maintain proper physiological function. The overall hypothesis of this proposal is that health is an active process that includes the induction of physiological mechanisms coordinated by microbes. By understanding the physiological mechanisms our bodies encode and how microbes coordinate these processes to maintain health, treatments that work to extend health-span and lifespan by overriding physiological decline can be developed, enabling patients to stay healthy despite infection. This application proposes a new paradigm for studying disease, where whole animal models, evolutionary principles and host- microbe interactions are used to define the properties and fundamental principles governing health. The work resulting from this application will establish a new conceptual framework and approaches in which to mechanistically understand what it means to be healthy and how this can be applied to treat diseases.

抽象的 治疗疾病的新视角。我们治疗疾病的方法之间存在脱节 以及我们对保持我们健康的机制的理解；这需要改变。过去的五十年 生物学研究通过减少 有机体及其组成部分，以便了解这些部分如何发生功能障碍的复杂细节 导致疾病。然而，这种方法的一个重大限制是，生理学不存在于 隔离;当一个系统出现故障时，整个身体都会受到影响。第二个问题是 使这种方法复杂化的是，目前治疗疾病的方法主要涉及阻断致病菌 反应而不是诱导有助于维持健康的途径。造成这种情况的原因有两个：1） 科学家研究的是疾病，而不是健康，因此不了解促进健康的机制； 2) 人们普遍认为，阻断致病反应将使患者恢复健康 状态，这不一定是真的。因此，问题不是我们应该如何治疗疾病，而是 应该问的是，“如何保持健康？” 理解并最终操纵所有之间发生的复杂的多向相互作用 根据我们的生理学，本申请提出了一种新颖的方法。该方法基于 了解身体及其驻留微生物群共同进化，依赖于所有微生物之间的交流 生理学，以维持正常的生理功能。该提案的总体假设是 健康是一个主动的过程，包括由微生物协调的生理机制的诱导。 通过了解我们身体编码的生理机制以及微生物如何协调这些机制 维持健康的过程，通过压倒一切来延长健康寿命和寿命的治疗 生理衰退可以发生，使患者在感染的情况下仍能保持健康。这个应用程序 提出了一种研究疾病的新范式，其中整个动物模型、进化原理和宿主 微生物相互作用用于定义健康的特性和基本原则。工作 该应用程序的结果将建立一个新的概念框架和方法 机械地理解健康意味着什么以及如何将其应用于治疗疾病。

项目成果

Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen.

• DOI: 10.1126/sciadv.adg8719
• 发表时间: 2023-06-23
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Chen, Grischa Y.;Thorup, Natalia R.;Miller, Abigail J.;Li, Yao-Cheng;Ayres, Janelle S.
• 通讯作者: Ayres, Janelle S.