title: Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma.
abstract: Arsenic is a carcinogenic environmental factor found in food and drinking water around the world. The mechanisms in which arsenic alters homeostasis are not fully understood. Over the past few decades, light has been shed on varying mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe perturbations, genotoxic effects, and epigenetic modification. Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide (LPS) leading to uncontained inflammation. Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma. Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification. The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers. These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.
authors.affiliation: Department of Physiology and Neurobiology, The Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Choiniere
authors.affiliation: Department of Physiology and Neurobiology, The Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA; Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT 06520, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
keywords: Arsenic; Epigenetics; Gut microbiota; Hepatocellular carcinoma; Lipopolysaccharide; Liver cancer; Microbiome