Effectiveness and mechanism of different molecular weight hyaluronic acid in repairing intestinal barrier function

Post-intensive care syndrome (PICS) presents significant clinical challenges due to impaired intestinal barrier function. This study investigated the molecular weight-dependent therapeutic efficacy of Hyaluronic Acid (HA) in a murine PICS model induced by cecal ligation and puncture (CLP). Mice were treated with HAs of varying molecular weights. In vivo fluorescence tracing assessed HA-mediated restoration of intestinal barrier integrity, while transcriptomic analysis and immunohistochemistry elucidated the underlying mechanisms. Results revealed that the differential efficacy of HA molecular weights correlated with their ability to block gut bacterial translocation. Transcriptomics and immunohistochemistry identified significant enrichment of peroxisome proliferator-activated receptor alpha/gamma (PPARα/γ) signaling pathways among HA-responsive genes. Crucially, the intensity of PPARα/γ immunostaining was directly and significantly associated with HA molecular weight (p < 0.001). The results indicate that high molecular weight hyaluronic acid (HA) more effectively improves intestinal barrier dysfunction, and transcriptomic and histological evidence suggests that the PPAR signaling pathway may be involved in this process.