阿尔茨海默病肠道细菌和真菌菌群结构和组成改变研究

Gut bacteriome and mycobiome dysbiosis in patients with Alzheimer's disease

目的探讨阿尔茨海默病(AD)患者肠道细菌组和真菌组的变化特征及其与宿主应答的互作关系。方法收集AD患者(n=39)和健康者(n=39)粪便样本和空腹血清样本,提取样本总DNA,采用MiSeq高通量测序分析样本中细菌和真菌的组成,并采用人27细胞因子联合检测试剂盒检测血清细胞因子水平。结果AD患者肠道细菌菌群多样性(Shannon指数)和丰富度(Observed OTUs,Chao 1指数,ACE指数)显著下降(P<0.05),产丁酸菌中的粪杆菌属(Faecalibacterium)和罗氏菌属(Roseburia)相对丰度显著降低(P<0.05),而产乳酸菌中的双歧杆菌属(Bifidobacterium)和乳杆菌属(Lactobacillus)显著增加(P<0.05)。肠道真菌菌群结构差异无统计学意义(P>0.05),但菌群组成中克柔假丝酵母菌(Candida xylopsoci)和埃切假丝酵母菌(Candida etchellsii)相对丰度显著降低(P<0.05),而裂褶菌(Schizophyllum commune)和变色栓菌(Trametes versicolor)显著增加(P<0.05)。AD患者血清中IFN-γ,MIP-1α和MCP-1显著降低,而TNF-α和IP-10显著升高(P<0.05);网络互作分析发现,AD肠道关键功能细菌、真菌和炎症标志物的互作网络更为复杂。结论AD患者肠道细菌组和真菌组发生显著改变,并与外周炎症因子相关,这为探索AD发病新机制和早诊早治提供新的线索。

Objective To observe the characteristics of gut bacteriome and mycobiome in Alzheimer's disease(AD)patients and their interaction with host immune response.Methods Fecal and fasting serum samples were collected from AD patients(n=39)and healthy subjects(n=39),and bacterial genomic DNA from fecal samples was extracted.MiSeq high-throughput sequencing was used to analyze the gut bacteriome and mycobiome,and the levels of cytokines in serum were detected using Bio-Plex Pro Human Cytokine 27-plex Assay.Results The diversity(Shannon index)and richness(Observed OTUs,Chao 1,and ACE indexes)of the gut bacterial community in AD patients significantly decreased(P<0.05).Certain butyrate-producing bacteria such as Faecalibacterium and Roseburia significantly reduced(P<0.05),while lactate-producing bacteria such as Bifidobacterium and Lactobacillus significantly increased(P<0.05).The structure of the gut mycobiome showed no significant changes(P>0.05),but specific fungal species such as Candida xylopsoci and Candida etchellsii significantly reduced(P<0.05),while others like Schizophyllum commune and Trametes versicolor significantly increased(P<0.05).In the AD patients,the levels of IFN-γ,MIP-1αand MCP-1 in serum significantly decreased,while TNF-αand IP-10 significantly increased(P<0.05).Network interaction analysis revealed a more complex interaction network among key functional bacteria,fungi,and inflammation markers in the gut of AD patients.Conclusion Significant changes occurred in the gut bacterial and fungal communities of AD patients,and are associated with peripheral inflammatory factors,which may provide new clues for exploring new mechanisms of pathogenesis and early diagnosis and treatment of AD.