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.

项目概要/摘要 环境健康科学和毒理学领域对这一问题的认识日益提高。 肠道微生物群对宿主对有毒化学物质暴露的反应至关重要。已知微生物群 直接和间接影响膳食和环境化学物质的毒性程度，并且已被证实 与多种疾病有关，包括代谢紊乱、癌症和炎症性疾病。小心 并进行严格的实验以确定微生物群影响环境的机制 化学暴露将使我们更全面地了解这些化学物质如何破坏宿主 微生物群相互作用，将对这些微生物群背后的关键信号通路产生新的见解 干扰和不良健康结果。重要的是，微生物群和环境化学物质的研究 可能提供关键见解，更好地为可能对人类健康产生积极影响的风险评估提供信息。在这个 R35 RIVER 提案中，我们计划跨三个创新且互补的主题开展工作，以解决 统一的假设是，环境化学物质暴露会扰乱宿主-肠道微生物群的相互作用，从而 对健康产生不利影响。首先，使用小鼠模型，我们将探讨生命早期接触的想法 环境化学物质影响晚年的健康结果（例如代谢紊乱、急性和慢性疾病） 炎症性肠病）通过宿主肠道微生物群轴的改变。其次，我们将研究如何 环境化学物质影响胃肠道的常见共生微生物，包括它们的 代谢活动和调节宿主生理的潜力。三是探索新路径。 微生物群控制和宿主生理过程的影响。为了实现这些目标，我们组建了一个 多元化、协作性和高度跨学科的团队，由生物化学、酶学、 免疫学、新陈代谢、微生物学、转录调控和毒理学。帕特森实验室拥有长期 沿着宿主-肠道微生物群轴做出独特和开创性发现的历史，因此处于有利位置 拥有尖端技术和方法、经验、创新理念以及开放/协作的 环境可以促进我们对宿主-肠道微生物群相互作用的理解并帮助推动该领域的发展 向前。从转化的角度来看，这些研究可能会带来新的饮食保护方法 通过设计新的益生菌/益生菌来降低环境毒性。