Positive effects of extracellular polysaccharides from Paecilomyces hepiali on immune-enhancing properties by regulating gut microbiota in cyclophosphamide-induced mice

Paecilomyces hepiali is a precious health-care edible medicinal fungus with rich polysaccharides and exhibits various biological activities. Polysaccharides from P. hepiali fermentation broth (PHP) exhibits good immunomodulatory activity; however, the mechanism underlying PHP-mediated regulation of immunity and gut microbiota remains unclear. To reveal the mechanisms, PHP of different doses were used to intervene cyclophosphamide (CTX)-induced immunosuppressive model mice. The results revealed that PHP facilitated the secretion of serum cytokines, increased the mRNA and protein expression of TLR4/NF-κB signaling pathway. Furthermore, it improved the physical barrier function of the intestine by upregulating the expression of tight junction proteins. PHP increased the proliferation of beneficial bacteria, including, Actinobacteriota, Alistipes, Candidatus_Saccharimonas and unclassified_Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria, Deferribacterota, Mucispirillum and Escherichia_Shigella, promoted the production of short-chain fatty acids, which were positively associated with immune traits. Thus, as an immune enhancer, PHP has the potential to regulate the intestinal immune response in immunosuppressed mice through modulating gut microbiota.