长测序技术揭示胃黏膜肠化生患者舌苔-胃黏膜菌群共生关系变化特征  

Long-read sequencing revealed alterations of microbial relationship between tongue coating and gastric mucosa in patients with gastric intestinal metaplasia

作　　者：吴剑平[1] 李美凤 华召来 陆斌 向娇 吴震峰[4] 张军峰[1] WU Jianping;LI Meifeng;HUA Zhaolai;LU Bin;XIANG Jiao;WU Zhenfeng;ZHANG Junfeng(School of Medicine,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210023,China;Institute of Tumour Prevention and Control,People's Hospital of Yangzhong City,Yangzhong,Jiangsu 212299,China;Department of Oncology,People's Hospital of Yangzhong City,Yangzhong,Jiangsu 212299,China;Department of Surgical Oncology,Jiangsu Province Hospital of Chinese Medicine,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210029,China)

机构地区：[1]南京中医药大学医学院,江苏南京210023 [2]扬中人民医院肿瘤防治研究所,江苏扬中212299 [3]扬中人民医院肿瘤科,江苏扬中212299 [4]南京中医药大学附属江苏省中医院消化系肿瘤外科,江苏南京210029

出　　处：《Digital Chinese Medicine》2023年第4期438-450,共13页数字中医药（英文）

基　　金：National Natural Science Foundation of China (81473458);Chinese Medicine Science and Technology Program of Jiangsu Province (MS2021003);Jiangsu Province Phase V"333"Scientific Research Project (BRA2020164)。

摘　　要：目的 探索胃黏膜肠化生(GIM)患者舌苔与胃黏膜菌群相关性。方法 本研究招募了1 360例志愿者参与上消化道癌筛查。收集舌苔和胃黏膜样本,基于16S r RNA基因长测序技术分析舌苔和胃黏膜菌群。利用Visual Genomics软件进行菌群分析,包括多样性、群落结构和线性判别分析(LEf Se)。Spar CC相关性分析用于构建共生网络,R软件图形化展示。结果 本研究人群包括44例癌前病变的GIM组和28例匹配的对照组(快速尿素酶试验阴性、无任何消化道症状的慢性浅表性胃炎患者)。GIM患者舌苔和胃黏膜菌群多样性无显著变化(P> 0.05),GIM患者舌苔-胃黏膜共现41–60个OTUs的个体比例(34.1%)显著高于对照组(25.0%)(P<0.05)。LEf Se分析显示,舌苔Prevotella melaninogenica和胃黏膜螺旋杆菌属的3个种(Helicobacter pylori、Helicobacter pylori XZ274和Helicobacter pylori 83)富集在GIM组。而且,在GIM组中,RUT阳性者舌苔-胃黏膜共享OTUs大于20的个体比例显著低于RUT阴性者(P<0.05),RUT阳性者胃黏膜Veillonella、 Pseudonocardia和Mesorhizobium的丰度显著低于RUT阴性者(P<0.05)。GIM组舌苔-胃黏膜菌群共生网络比对照组更复杂。在GIM组中,RUT阳性者舌苔-胃黏膜间的显著相关细菌对高于RUT阴性者。最后,RUT阴性者胃内3种螺旋杆菌属细菌(Helicobacter pylori、Helicobacter pylori XZ274和Helicobacter pylori 83)与PG-I/II比值呈显著负相关(P<0.05),RUT阳性者舌苔上两种菌株(Fusobacterium nucleatum subsp. nucleatum和Campylobacter showae)与PG-I/II比值呈显著负相关(P<0.05)。结论 GIM增强了舌苔和胃黏膜菌群的共生网络,为舌苔与胃之间的相关性提供了微生态学依据。Objective To explore the microbial correlation between oral tongue coating(TC)and gastric mucosa(GM)in patients with gastric intestinal metaplasia(GIM).Methods The present study recruited 1360 volunteers for upper gastrointestinal cancer screening.The microbiota in TC and GM were profiled by long-read sequencing of full-length 16S rRNA gene.The microbial diversity,community structure,and linear discriminant analysis effect size(LEfSe)were analyzed by the software Visual Genomics.SparCC correlation analysis was used to construct the commensal network and the graphical display was conducted by R software.Results The population included 44 patients with precancerous GIM,and 28 matched controls with negative rapid urease test(RUT)and non-symptomatic chronic superficial gastritis(CSG).No significant difference in diversity was observed between GIM patients and controls in TC or GM microbiota(P>0.05).Patients had a higher percentage of 41–60 co-occurring operational taxonomic units(OTUs)between TC and GM than controls(34.1%vs.25.0%)(P<0.05).The LEfSe showed that TC Prevotella melaninogenica and three gastric Helicobacter species(i.e.,Helicobacter pylori,Helicobacter pylori XZ274,and Helicobacter pylori 83)were enriched in patients with GIM.Furthermore,GIM patients with positive RUT had a lower percentage of co-occurring OTUs over 20(P<0.05),and lower abundances of gastric Veillonella,Pseudonocardia,and Mesorhizobium than those with negative RUT(P<0.05).The commensal network between TC and GM was more complex in GIM patients than in controls.GIM patients with positive RUT demonstrated more bacterial correlations between TC and GM than those with negative RUT.Finally,the serum ratio of PG-I/II was negatively correlated with three gastric Helicobacter species(Helicobacter pylori,Helicobacter pylori XZ274,and Helicobacter pylori 83)in patients with negative RUT(P<0.05),and negatively correlated with two TC species(Fusobacterium nucleatum subsp.nucleatum and Campylobacter showae)in patients with positive RUT(P<0.05).Concl

关 键 词：肠黏膜化生 舌苔 胃黏膜 菌群 共生关系 

分 类 号：R735[医药卫生—肿瘤]