title: Understanding the Molecular Mechanisms of Rifaximin in the Treatment of Gastrointestinal Disorders--A Focus on the Modulation of Host Tissue Function.
abstract: Rifaximin is a broad-spectrum oral antibiotic, exhibiting limited systemic absorption, that is used clinically to treat a variety of gastrointestinal disorders, including traveller's diarrhea, hepatic encephalopathy, irritable bowel syndrome, and the inflammatory bowel diseases. Rifaximin's antimicrobial properties, in the context of enteric infections, and its effects on the host's intestinal microbiota have been well characterized. More recently, it has been reported that rifaximin can modulate host tissue function through the activation of distinct molecular events. Within the gastrointestinal tract, rifaximin is a selective agonist of the pregnane X receptor (PXR), a nuclear receptor that regulates the expression of genes related to xenobiotic metabolism and drug detoxification. The PXR can also elicit immunomodulatory effects through its interaction with a variety of intracellular signaling cascades, including the nuclear factor kappa B and c-jun N-terminal kinase pathways. In this review, we will summarize the clinical uses of rifaximin and discuss its mechanism of action in relation to the modulation of the intestinal microbiota and the regulation of gastrointestinal host cell function, with a specific focus on PXR-dependent pathways.
authors.affiliation: 3330 Hospital Dr. NW - Health Sciences Room 1845; T2N 4N1, Canada. simon.hirota@ucalgary.ca.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Hirota
mesh_terms: D003967:Diarrhea / Q000188:drug therapy; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000188:drug therapy; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D012294:Rifamycins; D000078262:Rifaximin