자료유형  

 학위논문

Control Number  

0016935250

International Standard Book Number  

9798380722452

Dewey Decimal Classification Number  

300

Main Entry-Personal Name  

Bachas-Daunert, Stephanie.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2021

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2021

Physical Description  

1 online resource(264 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-05, Section: A.

General Note  

Advisor: Criddle, Craig;Fendorf, Scott;Relman, David;Bent, Stacey F.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2021.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Arsenic contamination of drinking water is a global environmental issue and public health crisis. In the US, 13 million people are exposed to levels exceeding US Water Quality Standards, and in Bangladesh, more than 25 million people are chronically exposed. Chronic ingestion can lead to arsenicosis, a disease with no effective treatment. By studying the role of the microbiome in arsenic metabolism, we aim to broaden traditional risk assessment and toxicology to incorporate consideration of host-associated microbiota. Our hypothesis is that arsenic ingestion alters the structure and function of gut microbiota and that differences in the microbiota contribute to observed variations in presence of arsenicosis, given similar levels and routes of exposure. Anaerobic bioreactors were employed to characterize the effects of exogenous arsenic on gut microbiota and their transformations of arsenic. We used HPLC-ICP-MS and x-ray experiments at the Stanford Synchrotron Radiation Lightsource to detect up to 96% conversion of As(V) to As(III) in a time series of samples from reactors inoculated with stool from healthy unexposed Palo Alto subjects and stool from a Bangladeshi cohort that included individuals chronically exposed, with and without disease, and individuals not exposed to arsenic in their water. In a subset of samples, we also detected production of methylated arsenicals DMA(V) and MMA(V) and trithioarsenite (AsS3 3-). We observed interindividual variability in conversion rates, methylation, and thiolation, with differences between Bangladeshi and Palo Alto subjects. These results illustrate the potential biotransformative capability of the gut microbiome and variation within and across cohorts. To our knowledge, this is the first application of microbiome-centric analysis in synchrotron studies. We also performed 16S rRNA gene sequencing of bioreactors and stool to characterize variations in taxonomic composition within and across cohorts. PCoA ordinations of bioreactor samples showed clustering by subject and cohort, with the exception of a Palo Alto Nepali male whose samples clustered with the Bangladeshi cohort. There were changes in taxonomic composition over time following exposure to arsenic. Using sparse LDA and sPLS-DA, we identified taxa that explain differences within cohort groups. Variation in Bangladeshi stool microbiota structure is correlated with cohort group (i.e., exposure and arsenic disease state) and nail and urinary arsenic. We identified taxa representative of each cohort group with phylogenetic tree-dependent and independent methods. There are group-specific taxa identifications robust to experimental type (i.e., stool cohort study or bioreactors). Future work includes metagenomic sequence-based assessments of bioreactors and stool from both cohorts to investigate differences in functional genes and pathways in the microbiome of healthy humans with no arsenic exposure and exposed individuals with/without arsenicosis. Correlations between microbiome structure and differences in biotransformation and/or disease state could lead to novel management strategies and interventions for communities exposed to arsenic.

Subject Added Entry-Topical Term  

Socioeconomic factors.

Subject Added Entry-Topical Term  

Womens health.

Subject Added Entry-Topical Term  

Toxicity.

Subject Added Entry-Topical Term  

Outdoor air quality.

Subject Added Entry-Topical Term  

Atmospheric sciences.

Subject Added Entry-Topical Term  

Public health.

Subject Added Entry-Topical Term  

Sociology.

Subject Added Entry-Topical Term  

Toxicology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 85-05A.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:639093