Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.

Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding their physiological functions on the gut microbiome. In this study, we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut microbiome using genetically engineered mice.

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.