Environmental Arsenic Exposure, Microbiome, and Human Health

环境砷暴露、微生物组和人类健康

• 批准号: 9113017
• 负责人: DAVID A. RELMAN
• 金额: $ 31.83万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9113017
• 关键词: Address; Affect; Agriculture; American; Anaerobic Bacteria; Arsenic; Bangladesh; Bangladeshi; Biochemistry; Bioreactors; Cardiovascular system; Childhood; Chronic; Clinical Data; Control Groups; Coupled; Couples; Detection; Development; Disease; Ecology; Environmental Exposure; Environmental Microbiology; Enzymes; Frequencies; Gene Targeting; Genes; Genomics; Goals; Hazardous Substances; Health; High Pressure Liquid Chromatography; Human; Individual; Industrialization; Ingestion; Intervention; Intoxication; Keratosis; Laboratories; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Malnutrition; Measurement; Measures; Melanosis; Metabolic Biotransformation; Metagenomics; Methods; Methyltransferase; Nail plate; Pattern; Pesticides; Plasma; Poison; Poisoning; Predisposition; Prevention; Prevention therapy; Principal Investigator; Public Health; Renal carcinoma; Research; Rice; Risk Assessment; Route; Sampling; Shotguns; Skin; Skin Cancer; Soil; Source; Southeastern Asia; Specimen; Spectrum Analysis; Structure; Taxonomy; Testing; Time; Toxic effect; United States; Urine; Variant; Water; Work; absorption; anthropogenesis; arsenate reductase; arsenite oxidase; cohort; contaminated water; data integration; detector; disease registry; effective therapy; gut microbiome; gut microbiota; interest; microbial; microbial community; microbiome; microbiota; multidisciplinary; novel; novel therapeutic intervention; novel therapeutics; public health relevance; pyrosequencing; rRNA Genes; residence; response; therapy design; water quality

DESCRIPTION (provided by applicant): Arsenic (As) contamination of soils and water occurs worldwide-including in the U.S.-originating from both environmental and anthropogenic sources. Naturally-occurring alluvial As contaminates groundwater in South and Southeast Asia, and has caused wide-scale poisoning of a susceptible and malnourished populace. Chronic As exposure affects over 25 million people in Bangladesh alone. Industrial sources of arsenic-e.g., arsenic- containing pesticides in agriculture-also contribute to global exposure. In the United States (US), As tops the hazardous substance priority list of the Agency for Toxic Substances and Disease Registries, and 13 million Americans are exposed to levels exceeding the US Water Quality Standards. Chronic exposure leads to arsenicosis, which includes melanosis, keratosis, and cardiovascular effects, as well as lung, bladder, kidney, and skin cancer. Chronic As exposure can also affect childhood intellectual function and development. There is no effective therapy for arsenicosis, emphasizing the importance of prevention and/or novel therapeutic approaches. Prevention requires effective risk-assessment, which also lays the groundwork for intervention design and treatment. The central hypothesis of this proposal is that As ingestion alters the structure and function of the human gut microbiota and that differences in the human gut microbiota contribute to the observed variation in the presence/absence of arsenicosis, given the same level and route of As environmental exposure through groundwater and rice. To test this hypothesis, the principal investigators will pursue the following specific aims: Specific Aim : To determine the effects of exogenous As on the gut microbiota and on the resulting transformation of As using anaerobic bioreactors in the absence/presence of arsenic-amended media; Specific Aim 2: To characterize the frequency and diversity of microbial genes related to As transformation in the gut microbiota of healthy humans with no As exposure, as well as of exposed individuals with/without arsenicosis; and Specific Aim 3: To characterize variations in taxonomic composition and functional potential of the gut microbiota of arsenic-exposed individuals with and without arsenicosis. To accomplish these specific aims they will make use of fecal specimens from non-exposed, healthy human individuals from the US, as well as fecal samples from subjects in Bangladesh with (1) chronic As exposure and arsenicosis, (2) chronic exposure and no arsenicosis, or (3) no exposure and no arsenicosis (control group). This multidisciplinary project lays the groundwork for microbiome-related risk assessment and further studies which will inform novel interventions for arsenicosis, a disease affecting millions worldwide.

描述（由申请人提供）：土壤和水的砷（AS）在全球范围内，包括来自环境和人为来源的美国。自然地将冲积物作为南亚和东南亚的地下水污染，并引起了易感和营养不良的民众的广泛中毒。仅在孟加拉国，慢性接触就会影响超过2500万人。砷的工业来源，农业中含有农药的砷，也有助于全球暴露。在美国（美国）， 作为有毒物质和疾病登记处机构的危险物质优先级，1300万美国人的水平超过了美国水质标准。慢性暴露会导致砷病，包括黑色素，角膜病和心血管效应，以及肺，膀胱，肾脏和皮肤癌。慢性接触也会影响儿童期智力功能和发展。没有有效的砷疗法治疗，强调了预防和/或新型治疗方法的重要性。预防需要有效的风险评估，这也为干预设计和治疗奠定了基础。该提议的中心假设是，随着摄入改变人类肠道菌群的结构和功能，人类肠道菌群的差异在存在/不存在砷中的差异中有助于观察到的变化，并且给定相同的水平和途径，并通过地下水和大米进行了AS环境暴露的水平和途径。为了检验这一假设，主要研究人员将追求以下特定目的：具体目的：确定外源性对肠道微生物群的影响以及在缺乏/存在砷的培养基的情况下使用厌氧生物反应器的AS的转化；具体目标2：表征与健康人的肠道微生物群体转化相关的微生物基因的频率和多样性，没有暴露，以及暴露的患有/没有砷的人的暴露者；和特定的目的3：表征砷暴露于有或没有砷的人的肠道菌群的分类学组成和功能潜力的变化。为了实现这些具体目标，它们将利用来自美国的非曝光，健康人的粪便标本，以及来自孟加拉国受试者的粪便样本，具有（1）慢性暴露和砷，（2）慢性暴露和无砷和无暴露和无暴露和无砷（对照组）（对照组）。这个多学科的项目为微生物组相关的风险评估和进一步的研究奠定了基础，这将为砷中毒的新干预提供依据，这是一种影响了全球数百万的疾病。