Environmental Chemical Impact on the Host-Microbiome Interaction

环境化学对宿主-微生物组相互作用的影响

• 批准号: 10641509
• 负责人: Andrew Patterson
• 金额: $ 93.15万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-13 至 2031-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641509
• 关键词: Acute; Address; Affect; Antibiotics; Biochemistry; Chemical Exposure; Chemicals; Chronic; Diet; Disease; Dose; Elderly; Environment; Environmental Health; Environmental Risk Factor; Enzymatic Biochemistry; Exercise; Exposure to; Gastrointestinal tract structure; Goals; Hazard Identification; Health; Human; Immune response; Immunology; Inflammatory; Inflammatory Bowel Diseases; Life Style; Malignant Neoplasms; Metabolic; Metabolic Diseases; Metabolism; Microbiology; Outcome; Pathway interactions; Physiological Processes; Physiology; Poison; Positioning Attribute; Probiotics; Recording of previous events; Regulation; Risk Assessment; Role; Seminal; Signal Pathway; Smoking; Social Interaction; Stress; Technology; Therapeutic; Toxic Environmental Substances; Toxic effect; Toxicology; Transcriptional Regulation; Work; Xenobiotics; collaborative environment; commensal microbes; design; dietary; early life exposure; environmental chemical; environmental chemical exposure; experience; gut microbiota; host microbiome; host microbiota; improved; innovation; insight; microbial; microbiome; microbiota; mouse model; novel; response; toxicant interaction

PROJECT SUMMARY/ABSTRACT There is an increasing level of appreciation in the fields of environmental health sciences and toxicology on the critical role of the gut microbiota on the host response to toxic chemical exposure. The microbiota is known to directly and indirectly influence the extent of toxicity of dietary and environmental chemicals, and has been implicated in a wide-range of diseases including metabolic disorders, cancer, and inflammatory diseases. Careful and rigorous experimentation to determine the mechanism by which the microbiota influences environmental chemical exposure will lead to a more complete understanding of how these chemicals disrupt the host- microbiota interaction and will generate novel insights into the key signaling pathways underlying those perturbations and adverse health outcomes. Importantly, studies of the microbiota and environmental chemicals may provide key insights that will better inform risk assessment that could positively impact human health. In this R35 RIVER proposal, we plan to work across three innovative and complementary themes to address the unifying hypothesis that environmental chemical exposure perturbs the host-gut microbiota interaction to adversely affect health. First, using mouse models, we will explore the idea that early-life exposure to environmental chemicals impacts later life health outcomes (e.g., metabolic disorders, acute and chronic inflammatory bowel disorders) via alterations in the host-gut microbiota axis. Second, we will examine how environmental chemicals impact common commensal microbes of the gastrointestinal tract including their metabolic activities and potential to modulate host physiology. Third, we will explore new pathways involved in microbiota control and influence of host physiologic processes. To achieve these goals, we have assembled a diverse, collaborative, and highly interdisciplinary team consisting of experts in biochemistry, enzymology, immunology, metabolism, microbiology, transcriptional regulation, and toxicology. The Patterson lab has a long history of making unique and seminal discoveries along the host-gut microbiota axis and thus is well-positioned with cutting-edge technology and approaches, experience, innovative ideas, and an open/collaborative environment to advance our understanding of the host-gut microbiota interaction and help to move the field forward. From a translational standpoint, these studies may lead to new protective approaches toward dietary and environmental toxicity through design of new pre/probiotics.

项目摘要/摘要 环境健康科学和毒理学领域的赞赏水平越来越高。 肠道菌群对宿主对有毒化学暴露的反应的关键作用。已知微生物群 直接和间接影响饮食和环境化学物质的毒性程度，并且已经存在 与包括代谢性疾病，癌症和炎症性疾病在内的广泛疾病有关。小心 和严格的实验，以确定微生物群会影响环境的机制 化学暴露将导致对这些化学物质如何破坏宿主的更全面了解 - 微生物群相互作用，并将对这些关键信号通路产生新的见解 扰动和不良健康结果。重要的是，对微生物群和环境化学物质的研究 可能会提供关键的见解，以更好地为风险评估提供可能对人类健康的积极影响。在这个 R35河提案，我们计划在三个创新和互补主题上工作，以解决 统一的假设，环境化学暴露使宿主形成微生物群的相互作用与 不利影响健康。首先，使用鼠标模型，我们将探讨以下想法 环境化学物质会影响以后的生活健康成果（例如，代谢性疾病，急性和慢性病 炎症性肠疾病）通过宿主型菌群轴的改变。第二，我们将研究如何 环境化学物质会影响胃肠道的常见共生微生物，包括其 代谢活动和调节宿主生理的潜力。第三，我们将探索涉及的新途径 宿主生理过程的微生物群控制和影响。为了实现这些目标，我们集会了 多样化，合作和高度跨学科的团队由生物化学专家，酶学专家组成， 免疫学，代谢，微生物学，转录调节和毒理学。帕特森实验室有很长的 沿宿主态微生物轴轴的独特和开创性发现的历史，因此是良好的 借助尖端的技术和方法，经验，创新思想以及开放/协作 环境促进我们对宿主型微生物群相互作用的理解，并有助于移动现场 向前。从翻译的角度来看，这些研究可能会导致饮食的新保护方法 通过设计新的预/益生菌的设计和环境毒性。