Academic journal article Environmental Health Perspectives

Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis

Academic journal article Environmental Health Perspectives

Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis

Article excerpt

Introduction

The human body is host to 100 trillion gut microbes, approximately 10 times more than all human cells (Ley et al. 2006). Ley et al. (2006) estimated that the approximately 500-1,000 species residing in the human gut encode 100-fold more unique genes than the human genome. The gut microbiota has important functions in metabolic processing, energy production, immune cell development, food digestion, epithelial homeostasis, and so forth (Young et al. 2008). Mounting evidence indicates that dysregulated gut microflora contributes in a significant way to a variety of diseases, including diabetes, obesity, cardiovascular diseases, allergies, inflammatory bowel disease, and others (Ley et al. 2005; Qin et al. 2012; Wang et al. 2011). For example, obese individuals exhibit a remarkable reduction in the abundance of Bacteroidetes and a relative increase in Firmicutes compared with lean individuals (Turnbaugh et al. 2006). Likewise, a metagenome-wide association study revealed that beneficial butyrate-producing bacteria are less abundant and that opportunistic pathogens are more abundant in individuals with diabetes than in healthy individuals (Qin et al. 2012). The gut microbiome evolves through several transitions during the first years of life and thereafter remains relatively constant if no significant perturbations occur. However, the composition of the gut microbiome is highly diverse, and this diversity can be readily affected by external factors such as environment, diet, bacterial/viral infection, and antibiotics. This raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration (dysbiosis) as a mechanism by which environmental agents exert their detrimental effects on human health.

Arsenic exposure affects large human populations worldwide, with contamination of drinking water by geological sources of inorganic arsenic being the primary route of exposure. Hundreds of millions of people around the world, especially in South and East Asia, drink water with arsenic levels that far exceed the 10-ug/L guideline established or accepted by the World Health Organization and the U.S. Environmental Protection Agency (EPA) (Hughes et al. 2011). In the United States, as many as 25 million people are estimated to drink water with an arsenic level > 10 [micro]g/L because private wells are not regulated by the U.S EPA and other agencies (Kozul et al. 2009). Arsenic exposure has been associated with a number of diseases such as skin, bladder, lung, and liver cancers and diabetes, as well as cardiovascular disorders (Hughes et al. 2011; Van de Wiele et al. 2010). More recently, arsenic exposure has been linked to an increased incidence of diabetes in animal models and human population studies (Paul et al. 2011). Numerous mechanisms have been proposed for arsenic-induced diseases, including interactions between arsenic and sulfur, oxidative stress, genotoxicity, altered DNA repair and signal transduction, cell proliferation, and epigenetics (Hou et al. 2012; Hughes et al. 2011; Ren et al. 2011; Smeester et al. 2011). Accumulating evidence indicates that perturbations of the gut microbiome and its influence on metabolic and physiological functions may play an important role in the development of human diseases. Given the essential role of the gut microbiome in a variety of aspects of human health coupled with the high toxicity of arsenic, there is a need to elucidate the effects of arsenic exposure on the gut microbiome and its functions. In particular, several seminal studies have reported interactions between the gut microbiome and environmental chemicals such as arsenic, mercury, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls (Choi et al. 2013; Liebert et al. 1997; Pinyayev et al. 2011; Van de Wiele et al. 2005, 2010).

The gut microbiome has profound roles in modulating host metabolism. For example, nondigestible carbohydrates are degraded via fermentation by the gut bacteria to yield energy for microbial growth and microbial end products that act as energy substrates, inflammation modulators, and signaling molecules (Holmes et al. …

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