H L DuPont1. 1. Center for Infectious Diseases, The University of Texas School of Public Health, Baylor College of Medicine, Kelsey Research Foundation, Houston, TX, USA.
Abstract
BACKGROUND: Disruption of the gut microbiota through use of systemic antimicrobials or activation of the mucosal inflammatory response by pathogens can cause dysregulation of the intestinal mucosa. AIM: To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea (TD). METHODS: A literature search was performed using the terms 'rifaximin' and 'L/105' in combination with the terms 'in vitro activity', 'diarrhea', 'microbiota' and 'gut flora'. RESULTS: Rifaximin has been traditionally identified as a nonsystemic, broad-spectrum, bactericidal antibiotic. Evidence shows that the activity of rifaximin against enteropathogens in this setting is likely enhanced by its increased solubility in the presence of bile acids in the small intestine. Results of clinical studies show that although rifaximin is efficacious in TD, a clinical cure often occurs without apparent bacterial eradication and with minimal effect on the gut microbiota, suggesting an effect of rifaximin other than direct antibiotic activity. CONCLUSIONS: Although definitive studies on the effect of rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation).
BACKGROUND: Disruption of the gut microbiota through use of systemic antimicrobials or activation of the mucosal inflammatory response by pathogens can cause dysregulation of the intestinal mucosa. AIM: To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea (TD). METHODS: A literature search was performed using the terms 'rifaximin' and 'L/105' in combination with the terms 'in vitro activity', 'diarrhea', 'microbiota' and 'gut flora'. RESULTS:Rifaximin has been traditionally identified as a nonsystemic, broad-spectrum, bactericidal antibiotic. Evidence shows that the activity of rifaximin against enteropathogens in this setting is likely enhanced by its increased solubility in the presence of bile acids in the small intestine. Results of clinical studies show that although rifaximin is efficacious in TD, a clinical cure often occurs without apparent bacterial eradication and with minimal effect on the gut microbiota, suggesting an effect of rifaximin other than direct antibiotic activity. CONCLUSIONS: Although definitive studies on the effect of rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation).
Authors: Daniela Weber; Robert R Jenq; Jonathan U Peled; Ying Taur; Andreas Hiergeist; Josef Koestler; Katja Dettmer; Markus Weber; Daniel Wolff; Joachim Hahn; Eric G Pamer; Wolfgang Herr; André Gessner; Peter J Oefner; Marcel R M van den Brink; Ernst Holler Journal: Biol Blood Marrow Transplant Date: 2017-02-14 Impact factor: 5.742
Authors: Danica Bajic; Adrian Niemann; Anna-Katharina Hillmer; Raquel Mejias-Luque; Sena Bluemel; Melissa Docampo; Maja C Funk; Elena Tonin; Michael Boutros; Bernd Schnabl; Dirk H Busch; Tsuyoshi Miki; Roland M Schmid; Marcel R M van den Brink; Markus Gerhard; Christoph K Stein-Thoeringer Journal: J Crohns Colitis Date: 2020-10-05 Impact factor: 9.071