POS0787 BERBERINE MODULATE LUPUS SYNDROME VIA THE REGULATION OF GUT MICROBIOTA IN MRL/LPR MICE

Background: Intestinal flora disorder and immune abnormalities have been reported in systemic lupus erythematosus (SLE) patients1,2. Berberine (BBR) showed significant effects in regulating the intestinal flora, repairing gut barriers and regulating immune cells3,4. While few reports mentioned the abnormal gut microbiota and metabolites in Chinese SLE patients. Objectives: Our investigation tried to illustrate the relationship between gut microbiota, intestinal metabolites and disease activity in Chinese SLE patients. And the effect of BBR to intestinal dysbacteriosis, multiple organ damages and over-activated immune system in MRL/Lpr mice. Methods: 16S high-throughput (16S rRNA) sequence, qRT-PCR and gas chromatography technology were used to determine the gut microbiota and metabolites in 104 SLE patients from Affiliated Hospital of Nantong University, China. BBR was orally treated to the MRL/Lpr mice in low, medium and high doses. After 6 weeks treatment, mice were sacrificed. Serum, faeces and organs were collected for further studies. Results: Chinese SLE patients showed higher abundance of Bacteroidetes and lower abundance of Firmcutes. The results of qRT-PCR showed high Firmcutes/Bacteroidetes (F/B) ratio of SLE patients. The F/B ratio was negative correlated with SLE disease activity index (SLEDA) score. Almost all the tested short-chain fatty acids (SCFAs) found statistically significant results in SLE and LN (lupus nephritis) patients, especially the propanoic acid and butyric. BBR altered the relative abundance of Bacteroides and Verrucomicrobia and the butyric acid content in colon of MRL/Lpr mice. The increase of tight junction protein also indicated the gut barrier was repaired by BBR. Treg and Tfr cells in spleen and mesenteric lymph node (MLN) were increased. These results revealed a positive therapeutic effect of berberine on SLE from gut microbiota to immune status. Conclusion: Our study highlights current status of intestinal dysbacteriosis in Chinese patients with SLE and differences in intestinal metabolites among patients with different disease states. The regulation of intestinal flora and the repairment of gut barrier by intestinal metabolites in BBR treated mice seemed to be the factor that directed the immune responses and disease outcomes. The ultimate goal of our study was to determine the beneficial effects of regulating the gut microbiota on the treatment of SLE. The application of berberine is a relatively safe and convenient way. In the coming investigations, we plan to focus on the study of berberine and its metabolites on intestinal function and systemic immunity. References: [1]Guo, M. et al. Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus. Gut microbes11, 1758-1773, doi:10.1080/19490976.2020.1768644 (2020). [2]Mu, Q. et al. Control of lupus nephritis by changes of gut microbiota. Microbiome5, 73, doi:10.1186/s40168-017-0300-8 (2017). [3]Habtemariam, S. Berberine pharmacology and the gut microbiota: A hidden therapeutic link. Pharmacological research155, 104722, doi:10.1016/j.phrs.2020.104722 (2020). [4]Cui, H. et al. Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon. Frontiers in pharmacology9, 571, doi:10.3389/fphar.2018.00571 (2018). Disclosure of Interests: None declared