College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Phytomedicine. 2021 Sep;90:153653. doi: 10.1016/j.phymed.2021.153653. Epub 2021 Jul 10.
Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive.
We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms.
C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis.
O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/β-catenin signaling via alleviating the overexpression of β-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis.
O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.
肠道微生物群在治疗炎症性肠病（IBD）和结肠炎相关癌症（CAC）中起着不可或缺的作用。作为传统药用真菌，先前的研究表明，与蛹虫草相比，冬虫夏草能更好地通过促进益生菌的体外生长来维持肠道健康。然而，冬虫夏草和蛹虫草的详细药理活性和临床疗效仍不清楚。
我们旨在评估冬虫夏草和蛹虫草对氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）处理的小鼠结肠炎相关肿瘤发生的不同作用，并探讨潜在的肠道微生物群依赖性机制。
使用 C57BL/6 小鼠（雄性，4 周龄）构建 AOM/DSS 诱导的 CAC 小鼠模型。将小鼠给予 0.6mg/g/d 的冬虫夏草或蛹虫草进行 12 周治疗。值得注意的是，使用粪便微生物移植（FMT）和抗生素处理来研究药用真菌、肠道微生物群和结肠肿瘤发生之间的复杂相互作用。
冬虫夏草治疗显著增加了体重和存活率，减少了结肠肿瘤数量，改善了结肠上皮组织损伤，恢复了隐窝结构，并减轻了 AOM/DSS 处理小鼠的结肠炎症。RT-qPCR 结果表明，冬虫夏草通过减轻邻近非癌组织中β-catenin、TCF4 和 c-Myc 基因的过表达，部分调节了 Wnt/β-catenin 信号通路。与蛹虫草相比，冬虫夏草表现出更好的抗肿瘤活性。肠道微生物群分析显示，冬虫夏草逆转了 AOM/DSS 诱导的肠道微生物多样性下降和结构紊乱。Spearman 相关性分析表明，冬虫夏草促进了 Parabacteroides goldsteinii 和 Bifidobacterium pseudolongum PV8-2 的生长，这与抗肿瘤活性和 SCFAs 的产生呈正相关。FMT 结合抗生素处理表明，来自冬虫夏草处理小鼠的水平粪便转移改善了肠道炎症并减轻了结肠炎相关的肿瘤发生，这与直接摄入冬虫夏草一致。
与蛹虫草相比，冬虫夏草能更好地减轻结肠炎相关的肿瘤发生。这些作用至少部分可能是由于益生菌（特别是 Parabacteroides goldsteinii 和 Bifidobacterium pseudolongum PV8-2）丰度的增加所致。
