Perioperative administration of fucoidan induced immune-suppressive changes that resulted in no beneficiary outcomes in postoperative neurocognitive recovery
For many of the versatile functions of polysaccharides as natural ingredients in human foods, the immunomodulatory and anti-inflammatory activities of fucoidan, partly owing to its high sulfate content, attracted extensive attention in its potential application in cancer therapy as well as in prevention of neurodegeneration. In this study, we characterized the impact of long-term supplementation of Undaria pinnatifida-derived fucoidan on the gene expression and immune cell abundance in mouse PBMCs. Despite the significantly increased Th17 cells and activated NK cells, naïve B cells were substantially reduced in the PBMCs in fucoidan mice.  Fucoidan supplementation induced prominent expression changes in genes associated with Th1/Th2 cell differentiation. Although fucoidan displayed a remarkable anti-inflammatory capacity in our mouse models, perioperative administration of fucoidan failed to show any noticeable beneficiary effect in relieving synaptic and cognitive dysfunction at the acute phase after surgery, which was believed to cause neurocognitive impairment by inducing neuroinflammation. Comparing with that of the mice with control diet, mitigated microglia activities including neuronal surveillance and phagocytosis were also observed in mice with perioperative administration of fucoidan. In addition, no influence on either basal level or surgery-induced oxidative stress was observed in mice with fucoidan supplementation. Given the complex features of inflammation as the first response to various detrimental situations, we proposed that the anti-inflammation potential of fucoidan was likely to induce an immune-suppressive change in the postoperative mouse brain and conferred unfavorable environment for the neurocognitive recovery at least at the acute phase after surgery. Overall design: This study employed a controlled animal experiment to investigate the impact of dietary fucoidan supplementation on peripheral immune transcriptomes and immune cell composition in mice. Peripheral blood mononuclear cells (PBMCs) were used as the biological material for transcriptomic profiling. Male C57BL/6J mice were assigned to experimental groups based on dietary intervention. Adult mice (8 weeks old) received either fucoidan supplementation or saline by daily oral gavage for one month while maintained on a standard basal diet. Fucoidan was derived from Undaria pinnatifida and administered at a dose of 200 mg/kg/day. Control animals received an equivalent volume of saline under identical conditions. At the end of the supplementation period, peripheral blood was collected by cardiac puncture, and PBMCs were isolated using density-gradient centrifugation. Total RNA extracted from PBMCs was subjected to high-throughput mRNA sequencing to characterize global gene expression profiles. The primary experimental variable was dietary supplementation with fucoidan versus saline control. The experimental design enabled comparison of PBMC transcriptomes between treatment groups to assess fucoidan-associated alterations in immune-related gene expression and inferred immune cell composition. All samples were processed in parallel using the same RNA extraction, library preparation, sequencing platform, and bioinformatics pipeline to minimize technical variability.