The microbiome plays an essential role in the health and onset of diseases in all animals, including humans. The microbiome has emerged as a central theme in environmental toxicology because microbes interact with the host immune system in addition to its role in chemical detoxification. Pathophysiological changes in the gastrointestinal tissue caused by ingested chemicals and metabolites generated from microbial biodegradation can lead to systemic adverse effects. The present critical review dissects what we know about the impacts of environmental contaminants on the microbiome of aquatic species, with special emphasis on the gut microbiome. We highlight some of the known major gut epithelium proteins in vertebrate hosts that are targets for chemical perturbation, proteins that also directly cross-talk with the microbiome. These proteins may act as molecular initiators for altered gut function, and we propose a general framework for an adverse outcome pathway that considers gut dysbiosis as a major contributing factor to adverse apical endpoints. We present 2 case studies, nanomaterials and hydrocarbons, with special emphasis on the Deepwater Horizon oil spill, to illustrate how investigations into the microbiome can improve understanding of adverse outcomes. Lastly, we present strategies to functionally relate chemical-induced gut dysbiosis with adverse outcomes because this is required to demonstrate cause-effect relationships. Further investigations into the toxicant-microbiome relationship may prove to be a major breakthrough for improving animal and human health. Environ Toxicol Chem 2018;37:2758-2775. © 2018 SETAC.

Center for Environmental and Human Toxicology University of Florida Gainesville Florida USA

Department of Environmental and Global Health College of Public Health and Health Professions University of Florida Gainesville Florida USA

Department of Physiological Sciences College of Veterinary Medicine University of Florida Gainesville Florida USA

Division of Coastal Sciences School of Ocean Science and Engineering University of Southern Mississippi Gulfport Mississippi USA

Genetics Institute University of Florida Gainesville Florida USA

Research Centre for Toxic Compounds in the Environment Faculty of Science Masaryk University Brno Czech Republic

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