Comprehensive Evaluation of GLP1 Receptor Agonists in Modulating Inflammatory Pathways and Gut Microbiota

This study provides a detailed examination of the anti-inflammatory effects of GLP-1 receptor agonists (GLP-1RAs), employing an integrative approach that combines multi-omics analysis with in vivo and in vitro experiments. The results showed a significant decrease in pro-inflammatory cytokines (−42%±3.5%, p<0.001) alongside a notable increase in anti-inflammatory markers (+38%±4.2%, p<0.001). Additionally, the intervention induced substantial restructuring of the gut microbiota, characterized by a 2.8-fold enrichment of Faecalibacterium prausnitzii (p<0.01) and a 2.1-fold increase in Roseburia spp. (p<0.05), together with an increase in short-chain fatty acids level, especially butyrate (+35%, p<0.01). These changes were closely related to improved cytokine regulation and enhanced metabolic activity. Comparative analyses further showed that GLP-1RAs exhibit better efficacy in reducing inflammatory markers relative to NSAIDs, as evidenced by lower cytokine levels and inflammation scores across both animal models and cell culture systems (p<0.05). Transcriptomic profiling identified 154 differentially expressed genes, with the upregulation of key anti-inflammatory pathways and the downregulation of pro-inflammatory mediators. The findings highlight the potential of GLP-1RAs as a targeted therapy for systemic inflammation, leveraging their effects on cytokine modulation, gut microbiota composition and metabolic pathways. Future studies should focus on optimizing GLP-1RA-based interventions by exploring their long-term effects and potential synergies with microbiota-directed therapies for chronic inflammatory conditions.