季节性H3N2亚型流感病毒感染患者中医证型与口咽部微生物的相关性研究  

Correlation Study Between Syndrome of Chinese Medicine and Oropharyngeal Microbiome of Seasonal Influenza(H3N2)

作　　者：张磊 卢幼然 郭玉红[3,4] 赵京霞 田敬华 徐霄龙[4,5] 吕小琴[7] 狄浩然 王晓鹏[8] 刘清泉 ZHANG Lei;LU You-ran;GUO Yu-hong;ZHAO Jing-xia;TIAN Jing-hua;XU Xiao-long;LU Xiao-qin;DI Hao-ran;WANG Xiao-peng;LIU Qing-quan(Emergency Department,Yanqing Hospital of Traditional Chinese Medicine,Beijing,102100;Respiratory Department,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing,100010;Medical Department,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing,100010;Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases,Beijing,100010;Beijing Institute of Traditional Chinese Medicine,Beijing,100010;Clinical Laboratory,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing,100010;Traditional Chinese Medicine Department,Children's Hospital,Capital Institute of Pediatrics,100020;Respiratory Department,Shunyi Hospital of Traditional Chinese Medicine,Beijing,101300;Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijingi 100010)

机构地区：[1]北京中医医院延庆医院急诊科,北京102100 [2]首都医科大学附属北京中医医院呼吸科,北京100010 [3]首都医科大学附属北京中医医院医务处,北京100010 [4]中医感染性疾病基础研究北京市重点实验室,北京100010 [5]北京市中医研究所,北京100010 [6]首都医科大学附属北京中医医院检验科,北京100010 [7]首都儿科研究所附属儿童医院中医科,北京100020 [8]北京中医医院顺义中医院呼吸科,北京101300 [9]首都医科大学附属北京中医医院,北京100010

出　　处：《中国中西医结合杂志》2020年第12期1439-1447,共9页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：北京市科技计划(No.Z114100006014056);北京市医院管理局重点医学专业发展计划(No.ZYLX201611);国家自然科学基金资助项目(No.81673934);国家科技重大专项(No.2017ZX10305501001);中国北京自然科学基金资助项目(No.7192083)。

摘　　要：目的研究患者感染H3N2流感病毒后口腔微生物群与中医证型的相关性。方法从1124例流感样患者和10名健康者的口咽部采集咽拭子样本,采用RT-PCR进行筛查,最终纳入117例H3N2阳性患者为H3N2组,10名健康者为对照组。根据中医证候分型,将H3N2组阳性患者分为风热组、风寒组和外寒里热组,每组39例。对H3N2阳性样本及健康者进行二代测序分析,比较H3N2流感病毒感染后患者与健康者口咽部微生物差异及不同中医证型H3N2患者口咽部微生物差异。结果与对照组比较,H3N2组拟杆菌门、酸杆菌门、芽单胞菌门、绿弯菌门和硝化螺旋菌门丰度较低(P<0.01);CHAO1、ACE和香农指数同样偏低(P<0.05)。风热组和风寒组变形菌门的丰度明显高于外寒里热组(P<0.01),厚壁菌门和拟杆菌门低于外寒里热组(P<0.01)。常见临床致病菌属,如不动杆菌属、伯克霍尔德菌-类伯克霍尔德菌属、克雷伯菌属、假单胞菌属,其丰度在外寒里热组患者中更高,而链球菌属在风热组患者中更高(P<0.05)。Beta多样性分析同样证实了各证型之间的显著微生物差异。同时,KEGG分析也显示风寒组/风热组和外寒里热组之间的显著差异(P<0.05)。结论H3N2感染影响了上呼吸道的微生态结构,中医证型与上呼吸道的微生物结构之间具有一定的相关性。Objective To explore the correlation between oropharyngeal microbiota and Chinese medicine(CM) syndrome type after infected by seasonal influenza(H3 N2). Methods The throat swabs were collected from 1 124 influenza-like participants and 10 healthy people, and then subiects were screened by RT-PCR. Finally, totally 117 H3 N2-positive patients in H3 N2 group and 10 healthy people in control group were recruited. The H3 N2-positive patients were divided into the syndrome of wind-heat(SWH) group, wind-cold(SWC) group, and external cold and internal heat(SECIH) group according to the taxonomy of CM, 39 in each group. Subsequently, the next-generation sequencing analysis of H3 N2-positive patients and healthy people were performed, and the the microbial differences between patients after IAV(H3 N2) infection and healthy people were compared, and the different micro-organisms in H3 N2 patients among 3 CM syndromes were also compared. Results Compared with control group, the abundance of Bacteroidetes, Acidobacteria, Gemmatimonadetes, Chloroflexi, and Nitrospirae were significantly lower in H3N2 group(P<0.01), CHAO1, ACE and Shannon Index were lower in H3N2 group(P<0.05). The abundance of dominant phylum Proteobacteria in SWH group and SWC group was higher than that in the SECIH group(P<0.01), while Firmicutes and Bacteroidetes were all higher in SECIH group(P<0.01). The common clinical pathogenic bacteria such as Acinetobacter, Burkholderia-paraburkholderia, Klebsiella, and Pseudomonas were higher in SECIH group, while the genus Streptococcus was higher in SWH group(P<0.05). Beta diversity analysis confirmed significant differences between syndromes. Simultaneously, discrepancies between SWH/SWC and SECIH were revealed by examining KEGG(P<0.05). ConclusionH3N2 could affect the micro-ecology in the upper respiratory tract, and the syndrome of CM is consistently associated with microbiome structure of the upper respiratory tract.

关 键 词：甲型流感病毒 H3N2亚型 微生物 中医证型 上呼吸道感染 

分 类 号：R254[医药卫生—中医内科学]