Rifaximin: beyond the traditional antibiotic activity

Antibiotics are mainly used in clinical practice for their activity against pathogens, but they also alter the composition of commensal gut microbial community. Rifaximin is a non-absorbable antibiotic with additional effects on the gut microbiota about which very little is known. It is still not clear to what extent rifaximin can be able to modulate gut microbiota composition and diversity in different clinical settings. Studies based on culture-dependent techniques revealed that rifaximin treatment promotes the growth of beneficial bacteria, such as Bifidobacteria and Lactobacilli. Accordingly, our metagenomic analysis carried out on patients with different gastrointestinal and liver diseases highlighted a significant increase in Lactobacilli after rifaximin treatment, persisting in the short time period. This result was independent of the disease background and was not accompanied by a significant alteration of the overall gut microbial ecology. This suggests that rifaximin can exert important eubiotic effects independently of the original disease, producing a favorable gut microbiota perturbation without changing its overall composition and diversity.

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“…This is in line with the evidence that rifaximin is able to promote the growth of beneficial bacteria [37]. …”

Section: Rifaximin: the Antibiotic With Eubiotic Effectssupporting

confidence: 77%

The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin

Ponziani

Scaldaferri

Petito

et al. 2016

Dig Dis

109

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“…It is poorly absorbed on oral administration (15) Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway and as such has an optimum safety profile. Apart from its antibiotic potential, rifaximin has also been studied for its anti-inflammatory effects; several studies have highlighted the anti-inflammatory potential of rifaximin, which is mainly attributed to the inhibition of the NF-κB signaling and NO release via activation of intestinal human pregnane X (PXR) receptors (16,17).…”

Section: Introductionmentioning

confidence: 99%

Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway

Esposito

Gigli

Seguella

et al. 2016

International Journal of Oncology

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Abstract. Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 µM) in the presence or absence of ketoconazole (10 µM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 µM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-α (HIF-1α), p70S6K and NF-κB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool. IntroductionColorectal cancer (CRC) represents one of the major causes of morbidity and mortality throughout the world and is the third most common form of human cancer worldwide (1,2). Like other forms of cancer, CRC is characterized by angiogenesis, which is a crucial event in promoting cancer growth, progression and metastasis (3). Among the various signaling molecules involved in the angiogenic process, vascular endothelial growth factor (VEGF) and nitric oxide (NO) are thought to be the key signaling molecules responsible for neo-vascularization (4-6). Once hypersecreted, VEGF binds to its type 2 receptor (VEGFR-2) and mediates the regulation of different pathways in the target cells, mainly the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (7,8) and the phosphop38 mitogen activated protein kinase (MAPK)-dependent activation of nuclear factor κB (NF-κB) (9,10). Activation of the NF-κB and Akt/mTOR pathways increases the levels of the inducible nitric oxide synthase (iNOS) isoform, leading to the release and accumulation of nitric oxide (NO) that acts as a pro-angiogenic stimulus on the blood vessels and favors neo-vascularization in solid tumors (5,11). Thus, targeting the angiogenic and mitogenic pathways is a rational and potentially effective strategy in the treatment of CRC (12).Rifaximin is a semi-synthetic antibiotic largely used fo...

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“…Однако пациент должен быть пре-дупрежден, что в случае возможного присоединения кишечной инфекции применение лоперамида не пока-зано и предпочтение должно отдаваться другим препа-ратам [35]. Учитывая тот факт, что СРК-Д достаточно часто имеет постинфекционный характер, в рамках лечения этого подтипа заболевания целесообразно использовать неабсорбируемый антибиотик рифаксимин, эффективно подавляющий избыточный рост бактерий в кишечнике [59,60]. Рифаксимин необратимо связывается с бета-субъединицей ДНК-зависимой РНК полимеразы, что приводит к ингибированию синтеза РНК и белков бакте-рий, способствуя снижению патогенной кишечной бакте-риальной нагрузки [60].…”

Section: заболевания кишечникаunclassified

“…Учитывая тот факт, что СРК-Д достаточно часто имеет постинфекционный характер, в рамках лечения этого подтипа заболевания целесообразно использовать неабсорбируемый антибиотик рифаксимин, эффективно подавляющий избыточный рост бактерий в кишечнике [59,60]. Рифаксимин необратимо связывается с бета-субъединицей ДНК-зависимой РНК полимеразы, что приводит к ингибированию синтеза РНК и белков бакте-рий, способствуя снижению патогенной кишечной бакте-риальной нагрузки [60]. Данный механизм действия особенно актуален при СРК-Д, так как при этом феноти-пе заболевания отмечаются достоверные альтерации кишечного микробиома, заключающиеся в количествен-ном снижении семейств Ruminococcaceae, Erysipelotrichaceae, Methanobacteriaceae и повышении условно-патогенных микроорганизмов, обладающих газопроду-цирующими свойствами [61,62].…”

Section: заболевания кишечникаunclassified