Cinnamomum cassia Modulates Key Players of Gut–Liver Axis in Murine Lupus

<b>Background</b>: Systemic lupus erythematosus is a multi-faceted auto-immune disease. Growing evidence points to gut permeability and microbiota as key players in the development of the disease. <i>Cinnamomum cassia</i> is gaining attention as a potential modifier of the gut and liver health. We aim in this study to explore the effect of cinnamon on key elements of the gut-liver axis in imiquimod-induced lupus. <b>Methods:</b> Female C57BL/6J mice were stratified into five experimental groups: sham, sham plus cinnamon, lupus, lupus with cinnamon treatment, and lupus with pre- and post-induction cinnamon treatment. Lupus was induced through application of 1.25 mg of 5% imiquimod cream to the right ear, three times per week over six weeks. <i>Cinnamomum cassia</i> was given orally at 200 mg/kg, five days weekly. High-Throughput Sequencing of Bacterial 16S rRNA Gene was used on fecal samples with subsequent bioinformatic analysis of microbiota. Western blot and antibody array were used to measure <i>E. coli</i> translocation, and hepatic inflammatory, oxidative, and apoptotic markers. <b>Results</b>: Cinnamon treatment mitigated the trend toward a lower Firmicutes/Bacteroidota ratio in the lupus mice. While not statistically significant, cinnamon also led to a decrease in Lachnospiraceae abundance. Interestingly, sham mice given cinnamon had more <i>Lactobacillus</i> and <i>Limosilactobacillus</i>. Furthermore, cinnamon effectively reversed the increase in <i>E. coli</i> protein in the liver and normalized the enhanced expression of TLR-7, p-NFκB/NFκB, SOD1 and SOD2 induced by lupus. <b>Conclusions</b>: <i>Cinnamomum cassia</i> modulates oxidative, inflammatory, and microbial elements of the gut-liver axis in lupus, offering a new perspective on lupus pathogenesis and potential nutritional interventions.