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Rifaximin decreases virulence of Crohn's disease-associated Escherichia coli and epithelial inflammatory responses.

TitleRifaximin decreases virulence of Crohn's disease-associated Escherichia coli and epithelial inflammatory responses.
Publication TypeJournal Article
Year of Publication2018
AuthorsDogan B, Fu J, Zhang S, Scherl EJ, Simpson KW
JournalJ Antibiot (Tokyo)
Volume71
Issue5
Pagination485-494
Date Published2018 05
ISSN1881-1469
KeywordsBacterial Adhesion, Caco-2 Cells, Crohn Disease, Cytokines, Dose-Response Relationship, Drug, Drug Resistance, Bacterial, Escherichia coli, Escherichia coli Infections, Gastrointestinal Agents, Gene Expression Regulation, Bacterial, Humans, Inflammation, Intestinal Mucosa, Macrophages, Rifaximin, Virulence Factors
Abstract

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.

DOI10.1038/s41429-017-0022-y
Alternate JournalJ Antibiot (Tokyo)
PubMed ID29410518