GLP1 receptor agonists attenuate systemic inflammation through microbiota mediated enrichment of Faecalibacterium prausnitzii and Roseburia spp

This study investigated the comparative anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and nonsteroidal anti-inflammatory drugs (NSAIDs), with a particular focus on microbiota-mediated mechanisms. A total of 120 participants were enrolled, including a GLP-1 RA group (n = 60) and an NSAID control group (n = 60). After 12 weeks of treatment, the GLP-1 RA group showed significant reductions in systemic inflammatory markers, with C-reactive protein (CRP) decreasing from 4.3 ± 0.6 to 2.1 ± 0.4 mg/L (p < 0.01), interleukin-6 (IL-6) decreasing from 3.6 ± 0.5 to 1.8 ± 0.3 pg/mL (p < 0.01), and tumor necrosis factor-α (TNF-α) decreasing from 18.2 ± 1.5 to 12.5 ± 1.2 pg/mL (p < 0.05). In contrast, the NSAID group exhibited only modest reductions in these markers without achieving normalization. Microbiome analysis revealed a significant post-treatment enrichment of Faecalibacterium prausnitzii (r = −0.46 with CRP, p < 0.001) and Roseburia spp. (r = −0.39 with CRP, p < 0.01) in the GLP-1 RA group, whereas NSAIDs showed no comparable effect. These findings establish a novel mechanistic link between incretin-based therapies and host immune homeostasis, highlighting the potential of GLP-1 RAs as systemic anti-inflammatory agents beyond their metabolic benefits.