Integration of Gut Microbiome and Serum Metabolomics Reveals the Anti-Inflammatory Mechanisms of Baicalin in CIA rats
The aim of this work is to investigate the impact of baicalin on serum metabolites, gut microbiome composition, and their correlation with Rheumatoid arthritis (RA) . Methods: Twenty-four Sprague-Dawley (SD) rats were randomly divided into four groups:Normal control group (Normal) ; CIA Model group (Model); Baicalin treatment group (Baicalin); Dexamethasone treatment group (DEX). The arthritis index scores, spleen index and inflammatory infiltration in ankle and knee synovial tissues were detected ;The percentages of splenic Th17 and Treg cells were measured by flow cytometry;Serum IL-6, IL-17 and IL-10 levels were detected via ELISA. Additionally, Gut microbiota composition on fecal samples was analyzed using 16S rRNA gene sequencing, and serum metabolites were analyzed by untargeted metabolomics via liquid chromatography-mass spectrometry (LC-MS). Results: Baicalin effectively mitigated RA-related inflammatory lesions, including relieved Joint Swelling, improved body weight, reduced arthritis Scores, and reduced inflammatory infiltration of the joint synovium. Baicalin decreased the proportion of splenic Th17 cells while elevating Treg cell ratio. Meanwhile, serum levels of pro-inflammatory IL-6 and IL-17A were downregulated, and anti-inflammatory IL-10 was upregulated.Moreover, 16S rDNA sequencing analysis of gut microbiome revealed adecreased abundance of Intestinimonas (p <0.05) and Ruminococcaceae UCG-005(p <0.05) in baicalin treated group rats compared with CIA modle group. In addition, the metabolomics analysis showed that baicalin treatment contributed to the upregulation of Toddalolactone and Prednisolone, and downregulation of Bavachalcone,Euchrenone b3, Fosfructose and Arugosin I. Moreover, the correlation analysis showed that Baicalin-induced differential gut microbiota and metabolites are associated with Th17/Treg balance and inflammatory cytokines.Conclusions: Baicalin can effectively mitigate RA through slowing down Inflammatory injury of articular synovium, modulating gut microbiota composition, and increasing beneficial metabolites.