There is a fundamental gap in understanding the role of environmental exposure-gut microbiome interactions in affecting human health. The microbiome of the human intestinal tract has a profound effect on human health through its key role in a wide range of host-related functions. Exposure to inorganic arsenic (iAs) is a significant public health issue worldwide and has been linked to a number of diseases, including cancers, metabolic disorders, cardiovascular diseases and impaired immune functions. Mounting evidence indicates that dysregulated gut microflora contribute significantly to many of these diseases, underscoring a potentially important role of the gut microbiome in arsenic-induced diseases. However, functional interaction between the gut microbiome and arsenic exposure is largely unexplored, except for the investigators' recent studies. Their central hypothesis is that the gut microbiome-arsenic interaction influences iAs toxicity. This hypothesis has been formulated on the basis of exciting preliminary data produced in the Principal Investigator's laboratory and will be tested by pursuing three specific aims, with the goal of defining the effects of iAs on the gut microbiome and its function and elucidating the role of gut microbiome community structures in mediating arsenic toxicity. The significance of this grant application lies in the fact that gut microbiome-exposure interaction is still largely unexplored despite the diverse and profound roles of the microbiome in human health. The investigators' proposed studies are also highly innovative and represent a paradigm shift in toxicology because they focus on gut microbiome perturbations as a novel mechanism of exposure-induced diseases and an unexplored risk factor responsible for individual susceptibility. The innovation of this grant application also stems from the novel application of integrated bioanalytical and computational tools to a systems-level study of a significant gut microbiome-exposure interaction. Findings from this study are expected to lay a foundation for future studies aiming at expanding our understanding of new mechanisms by which exposure to iAs leads to or exacerbates human disease: the role of the microbiome.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZES1)
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Lawler, Cindy P
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University of North Carolina Chapel Hill
Public Health & Prev Medicine
Schools of Public Health
Chapel Hill
United States
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Tu, Pengcheng; Bian, Xiaoming; Chi, Liang et al. (2018) Characterization of the Functional Changes in Mouse Gut Microbiome Associated with Increased Akkermansia muciniphila Population Modulated by Dietary Black Raspberries. ACS Omega 3:10927-10937
Chi, Liang; Bian, Xiaoming; Gao, Bei et al. (2018) Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice. Molecules 23:
Wu, Fen; Chi, Liang; Ru, Hongyu et al. (2018) Arsenic Exposure from Drinking Water and Urinary Metabolomics: Associations and Long-Term Reproducibility in Bangladesh Adults. Environ Health Perspect 126:017005
Chi, Liang; Gao, Bei; Tu, Pengcheng et al. (2018) Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome. Mamm Genome 29:63-79
Gao, Bei; Bian, Xiaoming; Chi, Liang et al. (2017) Editor's Highlight: OrganophosphateDiazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome. Toxicol Sci 157:354-364
Gao, Bei; Chi, Liang; Mahbub, Ridwan et al. (2017) Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways. Chem Res Toxicol 30:996-1005
Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan et al. (2017) Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions. Environ Health Perspect 125:198-206
Chi, Liang; Mahbub, Ridwan; Gao, Bei et al. (2017) Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner. Chem Res Toxicol 30:2110-2119
Bian, Xiaoming; Tu, Pengcheng; Chi, Liang et al. (2017) Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol 107:530-539
Chi, Liang; Gao, Bei; Bian, Xiaoming et al. (2017) Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice. Toxicol Appl Pharmacol 331:142-153

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