Inhibition of Intestinal Bacterial Translocation with Rifaximin Modulates Lamina propria Monocytic Cells Reactivity and Protects against Inflammation in a Rodent Model of Colitis

Abstract

Background: A modification of the intestinal flora and an increased bacterial translocation is a common finding in patients with inflammatory bowel disease as well as in animal model of colitis. Rifaximin, a non-absorbable derivative of rifamycin, is an effective antibiotic that acts by inhibiting bacterial ribonucleic acid synthesis. Aims: In the present study, we investigated the effect of the administration of rifaximin (10, 30 and 50 mg/kg/day) or prednisolone (10 mg/kg/day) in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: Colitis was induced in mice by intrarectal administration of TNBS (1.5 mg/mouse in 50% ethanol) and disease severity assessed clinically and by histologic scoring of colon damage, determination of interleukin (IL)-2, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α (protein and mRNA and myeloperoxidase (MPO) activity in the colon. Cytokines production by the lamina propria mononuclear cells (LPMC) and luminal bacteria were also measured. Results: Rifaximin administration (30 or 50 mg/kg/day) increased survival rates of colitic mice and reduced colitis severity as demonstrated by improvement of wasting syndrome, histologic scores, decrease in colon IL-2, IL-12, IFN-γ and TNF-α (protein and mRNA) levels, and diminished colon MPO activity. Rifaximin administration caused a significant reduction of colon bacterial translocation towards mesenteric lymph nodes. LPMC obtained from rifaximin-treated mice released significantly lower amount of IFN-γ in response to ex vivo stimulation with agonistic anti-CD3 and anti-CD28 antibodies. Rifaximin (50 mg/kg/day) significantly accelerates recovery in mice with established colitis. Conclusions: Luminal bacterial microflora plays a role in the pathogenesis of TNBS-induced colitis in mice. Rifaximin administration reduces the development of colitis and accelerates healing of established disease by preventing bacterial translocation.

The Role of Anti(myco)bacterial Interventions in the Management of IBD: Is There Evidence at All?

“…In all murine models of colitis, although the genetic defect or immunopathology may differ, the presence of normal enteric flora is required for full expression of inflammation [31]. Moreover, it has been demonstrated that the use of broad-spectrum antibiotics can treat and also prevent the onset of inflammation in almost all rodent models of acute and chronic colitis [32,33,34,35,36,37,38,39]. …”

Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells

“…Rifaximin has a broad-spectrum of activity against gram-positive and gram-negative aerobic and anaerobic enteric bacteria [36][37][38]. In addition to its anti-bacterial activity rifaximin exerts anti-inflammatory and immunomodulatory effects [38] in human tissues and in vivo.…”

Rifaximin, a Poorly Absorbed Antibiotic: Pharmacology and Clinical Potential

“…Investigations performed in rats with experimental acute pancreatitis [196] or ulcerative colitis [197] have shown that both rectal and oral administration of rifaximin decreased colonic bacterial translocation towards mesenteric lymph nodes. In the model of ANP [196] not only was the intra-abdominal spread of enteric bacteria ( fig.…”