胃癌患者脾胃虚弱证形成与舌苔菌群相关性研究

目的?探讨胃癌患者脾胃虚弱证形成的系统生物学机制。方法?招募22例胃癌脾胃虚弱证患者和32例体检者作为对照，基于16S rDNA和18S rDNA基因高通量测序分析舌苔细菌和真菌，电化学发光技术检测血清20种炎症因子，超高效液相色谱质谱联用技术（UPLC-MS）分析血清代谢组学。结果?与对照组相比，脾胃虚弱证患者舌苔厚壁菌门相对丰度显著升高，而拟杆菌门、变形菌门、梭杆菌门相对丰度降低（P<0.05）。线性判别分析（LDA）发现，芽孢杆菌属、肠球菌属、乳球菌属、沙雷氏菌属是胃癌脾胃虚弱证患者舌苔标志菌属。与对照组相比，胃癌脾胃虚弱证患者血清GM-CSF、IL-17α、IL-12/IL23P40和IL-6水平显著升高（P<0.05），而IL-5、TNF-β、IL-4水平显著降低（P<0.05），9种血清代谢分子（L-赖氨酸、二十碳五烯酸、L-天冬酰胺、溶血磷脂酰乙醇胺、磷脂酸、亚油酸、9-十六碳烯酸、α-亚麻酸和L-苯丙氨酸）显著上升（P<0.05）。Spearman相关性分析，IL-6、TNF-β、IL-5与卟啉单胞菌属、奈瑟菌属均显著相关（P<0.05），奈瑟菌属、梭杆菌属与9种血清代谢分子均显著负相关（P<0.05）。结论?胃癌脾胃虚弱证患者舌苔菌群结构差异与血清炎症因子和代谢组学相关，为阐明脾胃虚弱证的形成机制提供新的思路与方法。 

Study on the Correlation Between the Formation of Spleen-Stomach Deficiency Syndrome and Tongue Coating Microbiota in Patients with Gastric Cancer

OBJECTIVE?To explore the systemic biological mechanism of Spleen-Stomach Deficiency syndrome (SSD) in the patients with gastric cancer (GC). METHODS?22 GC patients with SSD and 32 healthy volunteers were recruited as controls. The tongue coating microbiota was analyzed by high-throughput sequencing based on 16S rDNA and 18S rDNA genes. Serum cytokines were detected by electrochemiluminescence， and serum metabolomics was analyzed by ultrahigh performance liquid chromatography-mass spectrometer (UPLC-MS). RESULTS?Compared with the controls， the GC patients had significantly increased coating Firmicutes and significantly decreased coating Bacteroidetes， Proteobacteria and Fusobacteria（P<0.05）.Linear discriminant analysis (LDA) presented that four coating bacterial genera (Bacillus， Enterococcus， Lactococcus and Serratia) enriched in GC patients. Compared with the controls， the serum levels of GM-CSF， IL-17α， IL-12/IL23P40 and IL-6 were significantly increased in GC patients (P<0.05)， the serum levels of IL-5， TNF-β and IL-4 were significantly decreased (P<0.05)， and nine serum metabolic molecules were significantly increased (P<0.05)， including L-lysine， eicosapentaenoic acid， L-asparagine， lysophosphatidylethanolamine， phosphatidic acid， linoleate， 9-hexadecanoic acid， α-linoleate， and L-phenylalanine. Spearman correlation analysis showed that IL-6， TNF-β and IL-5 were significantly correlated with coating Porphyromonas and Neisseria (P<0.05)， and Neisseria and Fusobacterium were negatively correlated with 9 serum metabolic molecules (P<0.05). CONCLUSION?The GC patients with SSD syndrome has altered tongue coating microbiota， which is linking with the different serum cytokines and metabolome. The data provides potential breakthrough point for clarifying the system biological mechanism of SSD syndrome.