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Author Dheer, Rishu ♦ Patterson, Jena ♦ Dudash, Mark ♦ Stachler, Elyse N. ♦ Bibby, Kyle J. ♦ Stolz, Donna B. ♦ Shiva, Sruti ♦ Wang, Zeneng ♦ Hazen, Stanley L. ♦ Barchowsky, Aaron ♦ Stolz, John F.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ABUNDANCE ♦ ARGININE ♦ ARSENATES ♦ ARSENIC ♦ BACTERIA ♦ CHRONIC EXPOSURE ♦ DRINKING WATER ♦ LARGE INTESTINE ♦ LIVER ♦ METABOLISM ♦ METABOLITES ♦ MICE ♦ NEOPLASMS ♦ NITRATES ♦ NITRITES ♦ OXIDOREDUCTASES ♦ PATHOGENESIS ♦ PHENOTYPE
Abstract Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes in microbial community structure, composition and nitrite reductase expression. • The profile of nitrogen and nitroamino acid change caused by arsenic may relect increased risk of cardiovascular pathogenesis.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-12-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 289
Issue Number 3


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