Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.
College of Basic Medical Science, Dalian Medical University, Dalian, China.
Phytomedicine. 2023 Dec;121:155082. doi: 10.1016/j.phymed.2023.155082. Epub 2023 Sep 11.
Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system.
We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms.
First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied.
Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier.
This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
益生菌发酵是改善中药（TCM）营养和功能特性的一种很有前途的策略。灵芝和莱菔子是两种著名的 TCM，已被证明有助于缓解免疫系统紊乱。然而，很少有研究从实验上探讨益生菌发酵灵芝和莱菔子对免疫系统的影响。
我们用益生菌混合物（长双歧杆菌、嗜酸乳杆菌和发酵乳杆菌）对灵芝和莱菔子进行体外发酵（GRFB），研究其对环磷酰胺（CTX）诱导的免疫抑制的改善作用，并探讨其可能的机制。
首先，通过高效液相色谱法鉴定 GRFB 中的不同成分。其次，在 CTX 处理的小鼠中评估其免疫刺激活性。最后，研究其可能的体外和体内机制。
灵芝和莱菔子的益生菌发酵改变了其一些化学成分，可能有助于提高 GRFB 缓解免疫抑制的能力。正如预期的那样，GRFB 通过增加脾淋巴细胞数量和调节血清和回肠细胞因子的分泌，有效改善 CTX 诱导的免疫抑制。GRFB 补充剂还通过上调紧密连接蛋白，有效改善 CTX 处理小鼠的肠道完整性。它还通过增加有益细菌的丰度和减少有害细菌的丰度来防止 CTX 诱导的肠道菌群失调。GRFB 可以在体外直接促进肠道免疫，但不促进全身免疫，表明 GRFB 的调节依赖于肠道微生物群。有趣的是，将 CTX 诱导免疫抑制的小鼠与 GRFB 处理的小鼠共同饲养促进了它们症状的恢复。GRFB 在体外增强 CTX 诱导的免疫抑制作用依赖于肠道微生物群。值得注意的是，京都基因与基因组百科全书分析表明，GRFB 重编程的微生物群在 DNA 损伤修复途径中显著富集，有助于修复肠道黏膜屏障。
与未发酵的灵芝和莱菔子相比，GRFB 可以更有效地促进肠道免疫，通过生物转化灵芝和莱菔子成分来操纵肠道微生物群，从而促进免疫刺激活性并修复免疫抑制引起的肠道屏障损伤，这是首次提出的观点。
