Cai Mengmeng, Xiao Ya, Lin Zhibing, Lu Jinmiao, Wang Xiaoyu, Rahman Sajid Ur, Zhu Shilan, Chen Xiaoyu, Gu Jialin, Ma Yuzhu, Chen Zhaoguo, Huo Jiege
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
Front Pharmacol. 2022 May 26;13:889181. doi: 10.3389/fphar.2022.889181. eCollection 2022.
This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4 and CD8 T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4 and CD8T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of , , , and were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of , , and than that in the non-intervention control group. and in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.
本研究旨在以抗肿瘤复方肠泰（FFCT）为治疗结直肠癌（CRC）的模型方剂，探讨肠道微生物群（GM）与血清代谢之间的关系。给荷瘤小鼠和正常小鼠施用不同剂量的FFCT。观察荷瘤小鼠的肿瘤体积。使用流式细胞仪测定小鼠血液、脾脏和肿瘤中CD4和CD8 T细胞的水平。分别使用16s RNA测序和液相色谱 - 质谱联用（LC/MS）检测小鼠粪便样本中的细菌微生物群以及FFCT处理小鼠和粪便微生物群移植小鼠的血清代谢组学。FFCT干预后小鼠肿瘤体积无显著减小。在FFCT干预下，CD4和CD8 T淋巴细胞水平显著升高。测定了结直肠癌荷瘤小鼠和健康小鼠的GM，两组之间的 、 、 和 的多样性和丰度存在显著差异。此外，我们发现FFCT干预后荷瘤小鼠中苦参碱、异姜烯酮B和亮菌甲素的水平显著降低，表明肿瘤诱导的肠道细菌生态失调可能影响FFCT的吸收和代谢。在FFCT干预下，移植CRC患者粪便的小鼠血清代谢物中与FFCT相关的比移植健康人粪便的小鼠少，表明GM可能是影响FFCT代谢的单一因素。此外，我们发现不同剂量FFCT处理的小鼠中 、 和 的丰度高于非干预对照组。与健康组相比，FFCT处理组中的 和 呈现相似趋势，表明FFCT可能通过调节结直肠癌荷瘤小鼠的肠道微生物群来纠正肠道微环境。荷瘤小鼠GM的生态失调减少了与FFCT相关的血清代谢物，而FFCT可以纠正结直肠癌荷瘤小鼠紊乱的GM以发挥疗效。
