Environmental Arsenic Exposure, Microbiome, and Human Health

环境砷暴露、微生物组和人类健康

• 批准号: 8606066
• 负责人: DAVID A. RELMAN
• 金额: $ 31.84万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8606066
• 关键词: Address; Affect; Agriculture; American; Arsenic; Bangladesh; Biochemistry; Bioreactors; Cardiovascular system; Childhood; Chronic; Clinical Data; Control Groups; Coupled; Couples; Detection; Development; Disease; Ecology; Environmental Exposure; Environmental Microbiology; Enzyme Gene; Enzymes; Frequencies; Gene Targeting; Genes; Genomics; Goals; Hazardous Substances; Health; High Pressure Liquid Chromatography; Human; Human Microbiome; Individual; Ingestion; Intervention; Intoxication; Keratosis; Laboratories; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Measurement; Measures; Melanosis; Metabolic Biotransformation; Metagenomics; Methods; Methyltransferase; Nail plate; Pattern; Pesticides; Plasma; Poison; Poisoning; Predisposition; Prevention; Principal Investigator; Public Health; Relative (related person); Renal carcinoma; Research; Rice; Risk Assessment; Route; Sampling; Shotguns; Skin; Skin Cancer; Soil; Source; Southeastern Asia; Specimen; Spectrum Analysis; Structure; Taxon; Testing; Time; Toxic effect; United States; Urine; Variant; Water; Work; absorption; anthropogenesis; arsenate reductase; arsenite oxidase; cohort; data integration; detector; disease registry; effective therapy; gut microbiota; interest; microbial; microbial community; microbiome; multidisciplinary; novel; novel therapeutic intervention; 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）：世界范围内（包括美国）土壤和水的砷 (As) 污染源自环境和人为来源。自然产生的冲积砷污染了南亚和东南亚的地下水，并导致易感人群和营养不良人群大范围中毒。仅孟加拉国就有超过 2500 万人受到慢性砷暴露的影响。砷的工业来源（例如农业中的含砷农药）也导致了全球砷暴露。在美国（US）， 作为有毒物质和疾病登记机构优先考虑的有害物质清单中的首位，1300 万美国人所接触的物质浓度超过了美国水质标准。长期接触砷会导致砷中毒，包括黑变病、角化病和心血管影响，以及肺癌、膀胱癌、肾癌和皮肤癌。慢性砷暴露还会影响儿童智力功能和发育。砷中毒没有有效的治疗方法，强调预防和/或新的治疗方法的重要性。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。该提案的中心假设是，砷的摄入会改变人类肠道微生物群的结构和功能，并且考虑到环境中砷的水平和途径相同，人类肠道微生物群的差异导致了砷中毒存在/不存在的观察到的变化。通过地下水和大米接触。为了检验这一假设，主要研究人员将追求以下具体目标： 具体目标：确定外源砷对肠道微生物群的影响，以及在不存在/存在砷改良培养基的情况下使用厌氧生物反应器对砷转化的影响；具体目标 2：表征未接触砷的健康人以及患有/未患有砷中毒的接触者肠道微生物群中与砷转化相关的微生物基因的频率和多样性；具体目标 3：表征患有或未患有砷中毒的砷暴露个体肠道微生物群的分类组成和功能潜力的变化。为了实现这些具体目标，他们将利用来自美国未接触砷的健康人的粪便样本，以及来自孟加拉国受试者的粪便样本，这些受试者患有（1）慢性砷暴露和砷中毒，（2）长期暴露且无砷中毒。砷中毒，或（3）无暴露且无砷中毒（对照组）。这个多学科项目为微生物组相关风险评估和进一步研究奠定了基础，这将为砷中毒（一种影响全世界数百万人的疾病）的新干预措施提供信息。