不同性传播途径的HIV感染者肠道微生态差异研究  

Differences of intestinal microecology in HIV-infected subjects with different sexual transmission routes

作　　者：吴雪琪 徐园红 阳凤娇 李青峰 何盛华 李樱杰 曾沛斌 WU Xue-qi;XU Yuan-hong;YANG Feng-jiao;LI Qing-feng;HE Sheng-hua;LI Ying-jie;ZENG Pei-bin(不详;West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院,四川成都610041 [2]成都市公共卫生临床医疗中心

出　　处：《现代预防医学》2022年第13期2430-2440,共11页Modern Preventive Medicine

基　　金：四川省科技厅重点研发(2018SZ0212,2018JY0383);四川省卫生和计划生育委员会(18PJ015)。

摘　　要：目的比较不同性传播途径的HIV感染者肠道微生态差异,为揭示与HIV感染相关的肠道细菌和真菌失调的全面特征提供研究基础。方法对36例HIV阳性感染者(HIV+),包括:男男性传播组(MSM)21例和异性性传播组(MSW)15例,及38例年龄、BMI与之相匹配的HIV阴性对照人群(HIV-)的粪便样本进行16S rRNA和ITS rRNA测序,测定外周血免疫细胞水平和10种免疫因子水平,采用生物信息学方法和秩和检验分析比较各组肠道微生态差异,并用Spearman秩相关分析肠道细菌-真菌相关性以及肠道微生物-免疫因子相关性。结果炎症相关因子TNF-α(H=11.680,P=0.003)、IL-22(H=10.139,P=0.006)和IL-10(H=6.039,P=0.048)在HIV+和HIV-间存在差异。在HIV+中观察到较低的细菌多样性和增加的真菌多样性。与MSW相比,MSM肠道菌群alpha多样性更高,肠道细菌魏斯氏菌属在组内富集(LDA=4.06,P=0.009)、而Ruminococcaceae.UCG.002属(LDA=3.47,P=0.022)、梭菌属(LDA=3.19,P=0.041),布劳特氏菌属(LDA=3.25,P=0.008)和Parasutterella属(LDA=2.89,P=0.048)减少;肠道真菌念珠菌属(LDA=4.73,P=0.039)和红酵母属(LDA=3.02,P=0.005)为优势菌属,蛙粪霉属(LDA=3.22,P=0.047)和圆酵母属(LDA=4.15,P=0.033)则减少。MSM肠道细菌和真菌间的关联揭示了可能的相互作用,例如魏斯氏菌属和念珠菌属(r=0.547,P=0.011)。此外,还发现韦荣氏球菌科细菌丰度与LBP水平呈负相关(r=-0.363,P=0.035)。结论性传播途径影响了HIV感染者肠道菌群特征,HIV感染与肠道微生态失调的深入机制有待进一步研究。Objective To compare the differences in the gut microecology of HIV-infected subjects with different sexual transmission routes,and to providie help for revealing the comprehensive characteristics of intestinal bacterial and fungal dysbiosis associated with HIV infection.Methods Fecal samples from 36 HIV-positive subjects(HIV+)(21 MSM and 15 MSW)and 38 HIV-negative controls(HIV-)with age and BMI matched were analyzed by 16 S rRNA and ITS rRNA sequencing.The immune cells and 10 cytokines in plasma peripheral blood were also quantitatively determined.The intestinal microecological differences among groups were analyzed and compared by bioinformatics and non-parametric test.Spearman’s rank order correlation was used to analyze gut bacteria-fungi associations and gut microbes-immune biomarkers associations.Results The inflammation-related cytokines TNF-α(H=11.680,P=0.003),IL-22(H=10.139,P=0.006)and IL-10(H=6.039,P=0.048)were significantly differed between HIV+and HIV-.Lower bacterial diversity and increased fungal diversity were observed in HIV+.Compared with MSW,the alpha diversity of the gut microbiota of MSM was higher,and gut bacteria Weisseria(LDA=4.06,P=0.009)were enriched within the group,while the genera Ruminococcaceae.UCG.002(LDA=3.47,P=0.023),Clostridium(LDA=3.19,P=0.041),Brautia(LDA=3.25,P=0.008)and Parasutterella(LDA=2.89,P=0.048)significantly decreased.MSM-specific gut fungi were characterized by enrichment of Candida(LDA=4.73,P=0.039)and Rhodotorula(LDA=3.02,P=0.005),and depletion of Basidiobolus(LDA=3.22,P=0.047)and Torula(LDA=4.15,P=0.033).Associations between MSM gut bacteria and fungi revealed possible interactions,such as Weisseria and Candida(r=0.547,P=0.011).Moreover,it was also found that the abundance of Veillonellaceae was negatively correlated with LBP levels(r=-0.363,P=0.035).Conclusion Sexual transmission routes affect the intestinal microbiota of HIV-infected subjects,and the comprehensive characteristics of HIV infection and intestinal microecological dysbiosis deserve further study.

关 键 词：艾滋病 肠道菌群 肠道真菌 免疫因子 

分 类 号：R117[医药卫生—公共卫生与预防医学] R512.91