肠道菌群-天然产物互作在免疫调节中的作用

Roles of gut microbiota-natural product interactions in immunomodulation

摘要:

肠道菌群与宿主免疫系统保持密切联系，微生物群落可通过多种途径影响免疫应答。大量研究证实，某些物质能够同步调节肠道菌群组成与宿主免疫反应，在免疫增强、抗炎及肠道稳态维持等方面发挥多种生物学功能。本文系统归纳了近3年国内外相关文献，首先详细阐述了肠道菌群通过多通路与宿主免疫相互作用的情况，进而重点归纳了通过肠道菌群途径发挥免疫调节功能(涵盖免疫增强与抗炎双重效应)的天然产物的最新研究。针对免疫失调性疾病，本文进一步阐明了天然产物通过优化肠道菌群结构、调控菌群-免疫信号通路[如核因子κB (nuclear factor kappa-B, NF-κB)、Toll样受体(Toll-like receptors, TLR)、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)等]互作、维持肠道屏障功能稳态及干预菌群代谢产物(如短链脂肪酸、色氨酸吲哚衍生物)等途径，实现对宿主免疫功能的精准调控。同时，本文探讨了肠道菌群通过代谢与生物转化作用将天然产物转化为高活性次级代谢产物，进而强化其免疫调节效应的具体过程。基于肠道菌群的天然产物免疫调节效应可能成为免疫相关疾病的潜在治疗策略。

Abstract:

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.