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各地，包括在美国-来源于环境和人类活动。自然发生的冲积砷污染了南亚和东南亚的地下水，并导致了易感和营养不良人群的大规模中毒。仅孟加拉国就有2 500多万人长期接触砷。砷的工业来源-例如，农业中的含砷农药也会导致全球接触。在美国（US）， 在有毒物质和疾病登记署的危险物质优先列表中，有1300万美国人暴露在超过美国水质标准的水平下。长期接触砷会导致砷中毒，包括黑变病、角化病和心血管效应，以及肺癌、膀胱癌、肾癌和皮肤癌。慢性砷暴露也会影响儿童的智力功能和发育。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，这也为干预措施的设计和治疗奠定了基础。该建议的核心假设是，由于摄入改变了人体肠道微生物群的结构和功能，人体肠道微生物群的差异有助于观察到的砷中毒存在/不存在的变化，由于通过地下水和大米的环境暴露的水平和途径相同。为了验证这一假设，主要研究人员将追求以下具体目标：具体目标：确定外源性As对肠道微生物群的影响以及在不存在/存在砷修正培养基的情况下使用厌氧生物反应器对As转化的影响;具体目标2：为了表征没有砷暴露的健康人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：描述有和没有砷中毒的砷暴露个体的肠道微生物群的分类组成和功能潜力的变化。为了实现这些特定目标，他们将使用来自美国的非暴露健康人类个体的粪便样本，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）慢性暴露和无砷中毒，或（3）无暴露和无砷中毒（对照组）。这个多学科项目为微生物群相关风险评估和进一步研究奠定了基础，这些研究将为砷中毒这种影响全球数百万人的疾病提供新的干预措施。