Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

Abstract

To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice’s stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice’s stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.

Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis

“…189 In support of our current results, a new research paper indicates that the fluoroquinolone levofloxacin effectively suppressed the synthesis of TNF-α, IL-17, IL-23, and JAK3 in murine models of inflammatory spondyloarthropathy. 190 Additionally, accumulating data reinforces levofloxacin's ability to block both TNF-α and IL-17 output, thereby decreasing neutrophil-mediated inflammation. 191,192 Similarly, the topical application of the levofloxacin antibiotic experiences inflammatory-lowering properties by hindering IL-8 and IL-6 concentrations within the pulmonary epithelium.…”

Investigating causal associations among gut microbiota, metabolites, and psoriatic arthritis: a Mendelian randomization study

“…A decrease in the abundance of Genus_ Odoribacter has been observed in patients suffering from rheumatoid arthritis ( Sun et al, 2019 ) and colitis ( Zhang et al, 2020 ). Conversely, an increase in the abundance of this strain has been identified in individuals with Spondyloarthritis ( González-Chávez et al, 2023 ). Additionally, the combined treatment with glucosamine and chondroitin sulfate has shown potential in improving rheumatoid arthritis in rats by effectively regulating the relative abundance of Genus_ Odoribacter ( Wang et al, 2023b ).…”