Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice

Abstract

Recently, accumulating evidence has suggested that gut microbiota may be involved in the occurrence and development of ankylosing spondylitis (AS). It has been suggested that rifaximin have the ability to modulate the gut bacterial communities, prevent inflammatory response, and modulate gut barrier function. The goal of this work is to evaluate the protective effects of rifaximin in fighting AS and to elucidate the potential underlying mechanism. Rifaximin were administered to the proteoglycan (PG)-induced AS mice for 4 consecutive weeks. The disease severity was measured with the clinical and histological of arthritis and spondylitis. Intestinal histopathological, pro-inflammatory cytokine levels and the intestinal mucosal barrier were evaluated. Then, western blot was performed to explore the toll-like receptor 4 (TLR-4) signal transducer and NF-κB expression. Stool samples were collected to analyze the differences in the gut microbiota via next-generation sequencing of 16S rDNA. We found that rifaximin significantly reduced the severity of AS and resulted in down-regulation of inflammatory factors, such as TNF-α, IL-6, IL-17A, and IL-23. Meanwhile, rifaximin prevented ileum histological alterations, restored intestinal barrier function and inhibited TLR-4/NF-κB signaling pathway activation. Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales . Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS.

Effective Combination Therapy of Angiotensin-II Receptor Blocker and Rifaximin for Hepatic Fibrosis in Rat Model of Nonalcoholic Steatohepatitis

“…In our previous clinical experiment, rifaximin caused only a slight change in intestinal flora [18]. However, the exact changes of the intestinal flora were not known [13,27]. Previous reports have shown that rifaximin inhibits the activation of NF-κB signaling pathway and downregulates the expression of inflammatory cytokines [27,28].…”

“…However, the exact changes of the intestinal flora were not known [13,27]. Previous reports have shown that rifaximin inhibits the activation of NF-κB signaling pathway and downregulates the expression of inflammatory cytokines [27,28]. Rifaximin could reduce the concentrations of TNF-α, IL-6, and endotoxin in patients with decompensated cirrhosis.…”

“…The mechanism of how rifaximin affects tight junction proteins is not well understood, however. Previous studies showed that rifaximin ameliorated visceral hypersensitivity and reduced intestinal permeability and increased TJP without altering microbiome [27]. Pregnane X receptor (PXR) is a ligand-activated transcriptional factor and nuclear receptor expressed universally along the gut-liver-axis [35].…”

“…Rifaximin could reduce the concentrations of TNF-α, IL-6, and endotoxin in patients with decompensated cirrhosis. Rifaximin slows down the fibrogenesis by suppressing the secretion of Kupffer cell-derived TGF-β, concerned with HSC activation through a paracrine mechanism [ 27 ]. In our current study, the prevention of the expression of hepatic TLR4, NF-κB, TGF-β by rifaximin highlights its suppressive effect on the TLR4/NF-κB signaling pathway in NASH rat model ( Figure 5 b–d).…”

Effects of Vitamin D3 on Intestinal Flora in a Mouse Model of Inflammatory Bowel Disease Treated with Rifaximin

“…Treatment with rifaximin can attenuated the imbalance of these microbiota [ 31 ]. Rifaximin can restore the unbalance of fecal microbiota in DSS-induced colitis mice [ 32 , 33 ]. In addition, rifaximin is a poorly absorbed semi-synthetic rifamycin antibiotic and gut-specific human PXR agonist [ 34 ].…”