Escherichia coli with an adherent and invasive pathotype (AIEC) is implicated in the pathogenesis of Crohn's disease (CD). Rifaximin improves symptoms in mild-to-moderate CD. It is unclear if this outcome is due to its effects on bacteria or intestinal epithelial inflammatory responses. We examined the effects of rifaximin on the growth and virulence of CD-associated E. coli and intestinal epithelial inflammatory responses. Seven well-characterized CD-associated E. coli strains (six AIEC, one non-AIEC; four rifaximin-resistant, three sensitive) were evaluated. We assessed the effects of rifaximin on CD-associated E. coli growth, adhesion to, and invasion of epithelial cells, virulence gene expression, motility, and survival in macrophages. Additionally, we determined the effects of rifaximin on intestinal epithelial inflammatory responses. In vitro rifaximin exerted a dose-dependent effect on the growth of sensitive strains but did not affect the growth of resistant strains. Rifaximin reduced adhesion, invasion, virulence gene expression and motility of CD-associated E. coli in a manner that was independent of its antimicrobial effect. Furthermore, rifaximin reduced IL-8 secretion from pregnane X receptor-expressing T84 colonic epithelial cells. The effect of rifaximin on adhesion was largely attributable to its action on bacteria, whereas decreases in invasion and cytokine secretion were due to its effect on the epithelium. In conclusion, our results show that rifaximin interferes with multiple steps implicated in host-AIEC interactions related to CD, including adhesion to, and invasion of epithelial cells, virulence gene expression, motility, and pro-inflammatory cytokine secretion. Further study is required to determine the relationship of these effects to clinical responses in CD patients.

中文翻译：

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利福昔明降低与克罗恩病相关的大肠杆菌的毒性和上皮炎症反应。

具有粘着性和侵入性病理型（AIEC）的大肠杆菌与克罗恩病（CD）的发病机制有关。利福昔明改善轻度至中度CD的症状。目前尚不清楚这种结果是否是由于其对细菌或肠道上皮炎症反应的影响。我们检查了利福昔明对CD相关大肠杆菌的生长和毒力以及肠上皮炎症反应的影响。评估了7个特征明确的CD相关的大肠杆菌菌株（6个AIEC，1个非AIEC； 4个耐利福昔明，3个敏感）。我们评估了利福昔明对CD相关的大肠杆菌生长，对上皮细胞的粘附和侵袭，毒力基因表达，运动性以及巨噬细胞存活的影响。此外，我们确定了利福昔明对肠上皮炎症反应的影响。体外利福昔明对敏感菌株的生长具有剂量依赖性，但不影响耐药菌株的生长。利福昔明以独立于其抗菌作用的方式降低了与CD相关的大肠杆菌的黏附，侵袭，毒力基因表达和运动性。此外，利福昔明减少了表达妊娠X受体的T84结肠上皮细胞的IL-8分泌。利福昔明对粘连的作用在很大程度上归因于其对细菌的作用，而侵袭和细胞因子分泌的减少归因于其对上皮的作用。总之，我们的结果表明，利福昔明干扰与CD相关的宿主-AIEC相互作用涉及的多个步骤，包括对上皮细胞的粘附和侵袭，毒力基因表达，运动性，和促炎性细胞因子的分泌。需要进一步研究以确定这些作用与CD患者临床反应的关系。