Roles of gut microbiota-natural product interactions in immunomodulation

The gut microbiota maintains a close dialogue with the host’s immune system, being capable of influencing immune responses through various pathways. It has been extensively documented that synchronous regulation of the gut microbiota and the host immune response exerts immunoenhancing, anti-inflammatory, and gut homeostasis-maintaining effects. By systematically reviewing the relevant literature published in the past three years, this article first elaborates on the interactions between the gut microbiota and the host’s immunity via multiple routes. It further summarizes recent studies on natural products that exert immunomodulatory functions (encompassing both immunoenhancing and anti-inflammatory actions) through gut microbiota pathways. Regarding immune dysregulation diseases, this review further elucidates how natural products achieve precise regulation of the host immune function by optimizing the gut microbiota structure, regulating microbiota-immune signaling pathways (e.g., NF-κB, TLR, and MAPK), maintaining intestinal barrier homeostasis, and intervening in microbiota-derived metabolites (such as short-chain fatty acids and tryptophan-indole derivatives). Additionally, this article discusses the process by which the gut microbiota enhances the immunomodulatory effects of natural products through metabolic conversion and biotransformation of natural products into highly active secondary metabolites. The immunoregulatory effects of natural products through the gut microbiota may become a potential therapeutic strategy for immune-related disorders.