Abstract
Rifaximin is a broad-spectrum antibiotic that ameliorates symptomatology in inflammatory/functional gastrointestinal disorders. We assessed changes in gut commensal microbiota (GCM) and Toll-like receptors (TLRs) associated to rifaximin treatment in mice. Adult C57BL/6NCrl mice were treated (7/14 days) with rifaximin (50/150 mg/mouse/day, PO). Luminal and wall-adhered ceco-colonic GCM were characterized by fluorescent in situ hybridization (FISH) and microbial profiles determined by terminal restriction fragment length polymorphism (T-RFLP). Colonic expression of TLR2/3/4/5/7 and immune-related markers was assessed (RT-qPCR). Regardless the period of treatment or the dose, rifaximin did not alter total bacterial counts or bacterial biodiversity. Only a modest increase in Bacteroides spp. (150 mg/1-week treatment) was detected. In control conditions, only Clostridium spp. and Bifidobacterium spp. were found attached to the colonic epithelium. Rifaximin showed a tendency to favour their adherence after a 1-week, but not 2-week, treatment period. Minor up-regulation in TLRs expression was observed. Only the 50 mg dose for 1-week led to a significant increase (by 3-fold) in TLR-4 expression. No changes in the expression of immune-related markers were observed. Rifaximin, although its antibacterial properties, induces minor changes in luminal and wall-adhered GCM in healthy mice. Moreover, no modulation of TLRs or local immune systems was observed. These findings, in normal conditions, do not rule out a modulatory role of rifaximin in inflammatory and or dysbiotic states of the gut.
Highlights
Rifaximin is a semi-synthetic non-absorbable antibiotic derived from rifamycin and with a broad-spectrum activity against Gram-positive and Gram-negative microorganisms proposed to act on the gut microenvironment [1,2]
Rifaximin showed to be effective for a variety of clinical uses and was initially approved for the treatment of traveler’s diarrhea caused by noninvasive strains of E. coli [1] and hepatic encephalopathy [4]
In the clinical practice, rifaximin is often prescribed for other gastrointestinal disorders, such as inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and diverticular disease, because of its theoretical capability to modulate the intestinal microbiota [6]
Summary
Rifaximin is a semi-synthetic non-absorbable antibiotic derived from rifamycin and with a broad-spectrum activity against Gram-positive and Gram-negative microorganisms proposed to act on the gut microenvironment [1,2]. Modifying the GCM is a therapeutic approach of growing interest for IBS In this context, rifaximin is used to treat SIBO and IBD [14], and, as mentioned above, was approved for the treatment of diarrhea-predominant IBS [15]. Pre-clinical evidence suggests that rifaximin might have anti-inflammatory activity, reducing mucosal inflammation and visceral hypersensitivity and restoring epithelial barrier function [17,18,19,20]. Whether or not these effects are secondary to its microbial actions or are direct, non-microbial-related, is still a matter of debate. To determine if changes in GCM might be associated to the local modulation of host immune-related responses, we assessed (real-time qPCR) changes in the expression of toll-like receptors (TLR)-dependent host-bacterial interaction systems and immune-related markers
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