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）：砷（As）污染的土壤和水发生在世界范围内，包括在美国，来自环境和人为来源。自然发生的冲积砷污染了南亚和东南亚的地下水，并造成了易感和营养不良人群的大规模中毒。仅在孟加拉国，慢性砷中毒就影响了2500多万人。工业来源的砷，例如：农业中使用的含砷农药也导致了全球暴露。在美国，