Gut microbiome: An intermediary to neurotoxicity

There is growing recognition that the gut microbiome is an important regulator for neurological functions. This review provides a summary on the role of gut microbiota in various neurological disorders including neurotoxicity induced by environmental stressors such as drugs, environmental contaminants, and dietary factors. We propose that the gut microbiome remotely senses and regulates CNS signaling through the following mechanisms: 1) intestinal bacteria-mediated biotransformation of neurotoxicants that alters the neuro-reactivity of the parent compounds; 2) altered production of neuro-reactive microbial metabolites following exposure to certain environmental stressors; 3) bi-directional communication within the gut-brain axis to alter the intestinal barrier integrity; and 4) regulation of mucosal immune function. Distinct microbial metabolites may enter systemic circulation and epigenetically reprogram the expression of host genes in the CNS, regulating neuroinflammation, cell survival, or cell death. We will also review the current tools for the study of the gut-brain axis and provide some suggestions to move this field forward in the future.