参白解毒方对结直肠腺瘤患者粪便代谢组学及肠道菌群分布的影响  

Effect of Shenbai Jiedu Prescription on Fecal Metabolomics and Intestinal Flora Distribution in Patients with Colorectal Adenoma

作　　者：张烨 倪明欣 沈梦 陶玉泉 李柳[2] 范旻旻 程海波 ZHANG Ye;NI Mingxin;SHEN Meng;TAO Yuquan;LI Liu;FAN Minmin;CHENG Haibo(Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China;Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor,The First Clinical College of Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学附属医院,江苏省中医院,南京210029 [2]南京中医药大学第一临床医学院,江苏省中医药防治肿瘤协同创新中心,南京210023

出　　处：《中国实验方剂学杂志》2024年第19期55-63,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2017YFC1700602);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202208);国家中医药管理局高水平中医药重点学科建设项目资助(国中医药人教函[2023]85号);江苏高校优势学科建设工程资助项目(PAPD);江苏高校“青蓝工程”资助项目(苏教师函[2023]27号);江苏省高等学校基础学科(自然科学)研究面上项目(22KJB310003);江苏省中医药科技发展计划项目(MS2022001)。

摘　　要：目的:观察参白解毒方对结直肠腺瘤患者粪便代谢组学及肠道菌群多样性分布的影响,探索其潜在的作用靶点。方法:共纳入21例结直肠腺瘤患者,连续服用参白解毒方4周,观察患者临床症状的改善,同时收集患者治疗前后粪便样本,采用液质联用(LC-MS)非靶向代谢组学及宏基因组学技术,探索参白解毒方可能作用的代谢通路及其对患者肠道菌群分布的影响。结果:患者服药后中医证候积分总分显著降低(P<0.01);非靶向代谢组学结果显示服药前及服药后代谢物分布各自呈聚集状态,共筛选出106种差异代谢产物(P<0.05);京都基因与基因组百科全书(KEGG)富集分析显示显著富集的代谢通路主要有精氨酸-脯氨酸代谢通路;铁死亡;甘氨酸,丝氨酸和苏氨酸代谢等通路(P<0.05);其中L-4-羟谷氨酸半醛、谷胱甘肽、焦磷酸异戊烯基、肌酸酐、4-乙酰氨基-2-氨基丁酸、胍乙酸几种差异代谢物参与上述代谢通路;将这几种代谢物与差异的肠道菌群进行关联分析,结果显示参白解毒方可通过调节Lachnoclostridium、Eggerthella及Dialister等肠道菌群干预结直肠腺瘤患者氨基酸及铁死亡等代谢通路(P<0.05)。结论:参白解毒方可能通过提高结直肠腺瘤患者肠道有益菌丰度、降低有害菌丰度;调节结直肠腺瘤患者氨基酸及铁死亡等代谢通路发挥改善患者临床症状作用。该研究可能为参白解毒方干预结直肠腺瘤复发及癌变提供一些研究思路及方向。Objective:To observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets.Method:A total of 21 patients diagnosed with colorectal adenoma were enrolled in this study.Following a four-week administration of Shenbai Jiedu prescription,their clinical symptoms were observed,and fecal samples of patients before and after treatment were collected.Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry(LC-MS)were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients.Result:The total scores of traditional Chinese medicine(TCM)syndromes of patients after drug administration decreased significantly(P<0.01).The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration,and a total of 106 differential metabolites were screened out(P<0.05).The Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis revealed that arginine-proline metabolism,ferroptosis,glycine,and serine and threonine metabolism were significantly enriched metabolic pathways(P<0.05).Notably,L-4-hydroxyglutamate semialdehyde,glutathione,isopentenyl pyrophosphate,creatinine,4-acetamido-2-aminobutanoic acid,and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways.Furthermore,the association between these metabolites and different intestinal flora was analyzed,and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium,Eggerthella,and Dialister(P<0.05).Conclusion:Shenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria,reducing the abundance of

关 键 词：结直肠腺瘤 参白解毒方 代谢组学 肠道菌群 宏基因组学 

分 类 号：R2-0[医药卫生—中医学] R22R242R285.5R574