Microbiota and Metabolomics Study of Vaginal Lavage Fluid in Patients with Persistent HR-HPV Infection with Dampness-Heat Syndrome
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摘要:
目的 对湿热下注证不同程度宫颈病变的高危型人乳头瘤病毒(High-risk human papillomavirus，HR-HPV)持续感染患者的阴道灌洗液进行代谢组学及菌群分析，寻找差异性代谢物和潜在的代谢通路，探寻HR-HPV持续感染引起的阴道微生态失衡与中医湿热下注证不同程度宫颈病变之间的联系。 方法 选取2020年5月至2020年7月于江苏省中医院妇科门诊就诊的HR-HPV持续感染、符合湿热下注证的患者共156例，采集阴道灌洗液用于16S rDNA基因测序和GC-MS代谢组学分析。 结果 阴道灌洗液共检测出了164种代谢产物，不同程度宫颈病变组的代谢模式有着显著差异，多种代谢产物与阴道菌群有显著关联性。其中牛磺酸、鸟嘌呤、尿酸等代谢产物含量在不同程度宫颈病变的HR-HPV持续感染湿热下注证患者中有明显的差异，牛磺酸与魏斯氏菌属等呈正相关，与棒杆菌属等呈负相关。其中可能涉及7条相关代谢通路。 结论 阴道灌洗液易于获得且无创，可作为不同程度宫颈病变的潜在诊断策略并揭示HPV的可能发病机制；随着宫颈病变进展，奇异菌属、纤毛菌属以及其他杂菌的丰度上升，链球菌属的丰度则下降；牛磺酸、鸟嘌呤、尿酸等代谢产物都与人体的免疫系统激活密切相关，宫颈阴道菌群可调节氨基酸、酯类、嘌呤、脂质的合成与分解，可能在激活炎症及免疫系统上起重大作用；HR-HPV持续感染湿热下注证可以改变患者的氨基酸、嘌呤、脂质等的代谢特征。 Abstract:OBJECTIVE To search for differential metabolites and potential metabolic pathways, and to reveal the relationship between continuous HR-HPV infection with vaginal microecological imbalance and TCM damp-heat syndrome with different degress of cervical lesions, the vaginal lavage fluid of patients who have continuous HR-HPV infection in the different degrees of cervical lesions with damp-heat syndrome is analyzed by metabolomics and 16S rDNA. METHODS A total of 156 patients with HR-HPV persistent infection who were admitted to gynecology department of Jiangsu Hospital of Traditional Chinese Medicine from May 2020 to July 2020 were selected. Vaginal lavage fluid was collected for 16S rDNA gene sequencing and GC-MS metabolomics analysis. RESULTS 164 known metabolites were detected in Vaginal lavage, HSIL group showed significant difference from other groups secretion metabolic model, and found that the contents of taurine, guanine, uric acid and other metabolites were significantly different in patients with HR-HPV persistent dampness and damp-heat down type with different degrees of cervical lesions, which may be involved in a total of 7 metabolic pathways. CONCLUSION Vaginal lavage fluid is easy to obtain and non-invasive, and has the potential to be used as a diagnostic tool to assist in the diagnosis of HPV pathogenesis and SIL progression, and has a great promoting effect on the prevention of cervical cancer. With the progress of cervical lesions, the abundance of mirabilis, ciliates and other miscellaneous bacteria increases, while the abundance of Streptococcus decreases. Taurine, guanine, uric acid and other metabolites are associated with the activation of the human immune system. The cervix vaginal flora may play a significant role in the activation of inflammation and the immune system by regulating the synthesis and decomposition of amino acids, esters, purines and lipids. The metabolic characteristics of amino acids, purines and lipids in patients with persistent HR-HPV infection can be changed by Damp-heat down type. -
Key words:
- HR-HPV /
- damp-heat down type /
- vaginal microecology /
- metabonomics
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图 4 阴道菌群对HR-HPV感染患者的代谢通路分析
注：宫颈阴道菌群影响LSIL发生的代谢途径：A1.Aminoacyl-tRNA biosynthesis；B1.Phenylalanine, tyrosine and tryptophan biosynthesis；C1.Alanine, aspartate and glutamate metabolism；D1.D-Glutamine and D-glutamate metabolism; E1.Arginine biosynthesis。宫颈阴道菌群影响HSIL发生的代谢途径：A2.Aminoacyl-tRNA biosynthesis；B2.Phenylalanine, tyrosine and tryptophan biosynthesis；C2.Alanine, aspartate and glutamate metabolism；D2.beta-Alanine metabolism; E2.Phenylalanine metabolism
表 1 3组患者年龄、孕次、产次比较 (x±s)
组别 例数 年龄/岁 孕次 产次 NILM组 78 35.60±7.843 2.40±1.761 1.12±0.581 LSIL组 52 37.50±9.648 2.04±1.414 0.94±0.639 HSIL组 26 38.08±7.494 2.27±1.343 1.12±0.711 
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