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

Front Cell Infect Microbiol. 2019 Mar 4:9:44. doi: 10.3389/fcimb.2019.00044. eCollection 2019.

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.

Keywords: ankylosing spondylitis; gut microbiota; inflammatory response; intestinal epithelial barrier; rifaximin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Cluster Analysis
  • Cytokines / analysis
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Microbiome / drug effects*
  • Immunologic Factors / analysis
  • Mice, Inbred BALB C
  • Microbiota / drug effects*
  • Phylogeny
  • RNA, Ribosomal, 16S / genetics
  • Rifaximin / administration & dosage*
  • Sequence Analysis, DNA
  • Severity of Illness Index
  • Spondylitis, Ankylosing / chemically induced
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / pathology*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • DNA, Bacterial
  • DNA, Ribosomal
  • Gastrointestinal Agents
  • Immunologic Factors
  • RNA, Ribosomal, 16S
  • Rifaximin