Use and Safety of Rifaximin in Children With Inflammatory Bowel Disease

Muniyappa, Pramodha; Gulati, Reema; Mohr, Franziska; Hupertz, Vera

doi:10.1097/mpg.0b013e3181a0d269

Cited by 34 publications

(16 citation statements)

References 15 publications

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“…In our study, the microbial communities are altered before the induction of disease, thereby allowing us to ascertain the effects of community changes on disease development. There is also evidence that the microbial community is important in persistence of bowel inflammation, indicated by antibiotic studies showing amelioration of inflammation after treatment [50,51]. Apart from this, we have little insight into the role of the microbiota in IBD.…”

Section: Discussionmentioning

confidence: 99%

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

et al. 2013

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BackgroundThe aberrant inflammation that is the hallmark of the inflammatory bowel diseases (IBD) is associated with several factors, including changes in the intestinal microbiota. Here, we confirmed that an intestinal microbiota is needed for development of typhlocolitis in Helicobacter hepaticus infected IL-10-/- C57BL/6 mice, and investigated the role of the microbiota in modulating disease.ResultsWe altered the murine microbiota by treatment with the antibiotics vancomycin or cefoperazone prior to H. hepaticus infection. Through surveys of the 16S rRNA encoding-gene, analyses of histology and changes in expression of host mediators, we correlated alterations in the microbiota with host responses. We found that resident microbes are essential for initiation of disease, as animals mono-associated with H. hepaticus did not develop colitis. Despite the requirement for an indigenous microbiota for the initiation of disease, the severity of disease was independent of antibiotic-induced changes in the microbial community structure. Despite differences in the expression of host inflammatory mediators associated with shifts in the microbiota, H. hepaticus infection led to similar histopathologic lesions in microbial communities exposed to either cefoperazone or vancomycin.ConclusionIn conclusion, we demonstrate that colitis due to H. hepaticus infection can be initiated and progress in the presence of several different microbial communities. Furthermore, H. hepaticus is the main driver of inflammation in this model, while the specific structure of the microbiota may modulate the host pathways that lead to chronic inflammation.

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Section: Discussionmentioning

confidence: 99%

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

et al. 2013

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“…Reduced SCD-1 results in lower levels of unsaturated lysophosphatidylcholine in plasma, which is among the most important anti-inflammatory unsaturated fatty acids 41 . Clinically, rifaximin appears to have more efficacy in the therapy of CD than do traditional medications used to treat IBD such as metronidazole and/or ciprofloxacin 42–43 , due in part to its well-tolerated and efficient effects in adult CD patients 44 as well as for pediatric IBD 45 . Several clinical trials demonstrated that rifaximin decreased intestinal permeability in adult/pediatric patients with gastrointestinal diseases, such as small intestine bacterial overgrowth 46 or tropical enteropathy 47 .…”

Section: Role Of Pxr In the Pathogenesis Of Ibdmentioning

confidence: 99%

Pregnane X receptor as a target for treatment of inflammatory bowel disorders

Cheng

Shah

Gonzalez

2012

Trends in Pharmacological Sciences

146

125

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Pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, has a major role in the induction of genes involved in drug transport and metabolism. Recent studies in mice have provided insight into a novel function for PXR in inflammatory bowel disease (IBD). The mechanisms of the protective effect of PXR activation on IBD is not fully established, but is due in part to the attenuation of nuclear factor kappa B (NF-κB) signaling that results in lower expression of proinflammatory cytokines. Recent clinical trials with the antibiotic rifaximin, a PXR agonist in the gastrointestinal system, have revealed its potential therapeutic value in the treatment of intestinal inflammation in humans. Thus, PXR may be a novel target for IBD therapy.

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“…Other studies revealed that two-thirds of adult patients with Crohn's disease entered remission after rifaximin therapy (Shafran and Burgunder, 2010). A retrospective review revealed a well tolerated and favorable role for rifaximin in pediatric IBD (Muniyappa et al, 2009;Trehan et al, 2009). However, the role of rifaximin in irritable bowel syndrome and IBD therapy and its mechanisms of action are not understood.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

Cheng

Shah²,

Ma³

et al. 2010

J Pharmacol Exp Ther

151

143

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Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS-and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor B (NF-B) target genes were markedly downregulated in hPXR mice by rifaximin treatment. In vitro NF-B reporter assays demonstrated inhibition of NF-B activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-B signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD.

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Use and Safety of Rifaximin in Children With Inflammatory Bowel Disease

Abstract: Rifaximin was well-tolerated and showed favorable results. Larger doses of rifaximin were statistically better for abdominal pain. Further studies are needed to evaluate efficacy and optimal dosing of rifaximin in this population.

Cited by 34 publications

References 15 publications

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

Pregnane X receptor as a target for treatment of inflammatory bowel disorders

Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

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