不同免疫重建状态的HIV感染者基线口腔菌群差异及相关性分析

Diversity and correlation analysis of baseline oral flora among HIV-infected patients with different immune reconstitution status

目的了解不同免疫重建状态下HIV感染者基线口腔菌群的差异,并分析该差异与免疫重建结果的相关性。方法2017年8月至2019年10月,以首都医科大学附属北京佑安医院的患者和健康志愿者为研究对象,采集口腔唾液样本并行16S rRNA测序,cART 2年后对HIV感染者进行随访并根据CD4细胞计数分组,应用R语言等软件进行差异及相关性分析。结果共纳入男性HIV感染者43人和健康对照组(HC)15人,其中HIV感染者根据cART 2年CD4细胞计数分为免疫重建不全组(INR)9人、中间组(M)9人、免疫重建良好组(IR)25人。四组患者在年龄(P=0.556)上差异无统计学意义。唾液多样性分析显示,INR、M、IR和HC四组间的β多样性差异有统计学意义(P=0.003),其中IR组口腔菌群丰富度显著增高。在属水平上,INR、IR和HC组丰度最高的5个优势菌属分布不同,且IR中富集的Treponema_2、Aggregatibacter菌属与CD4细胞计数和CD4/CD8细胞比值的升高呈正相关,而INR组中富集的Solobacterium菌属与CD4细胞计数的升高呈负相关。ROC曲线分析表明Treponema_2用于判别INR或IR状态的准确性较高。结论不同免疫重建状态下HIV感染者基线口腔菌群存在显著差异,不同的口腔菌群特征以及特殊的标志菌属(如Treponema_2等)可能是影响HIV感染者免疫重建的重要因素之一。

Objective This study aimed to investigate the differences in baseline oral microbiota among individuals infected with HIV with different immune reconstitution statuses and to analyze the correlation between these differences and immune reconstitution outcomes.Methods From August 2017 to October 2019,patients from Beijing You'an Hospital,Capital Medical University,and healthy volunteers were enrolled as research participants.Oral saliva samples were collected and subjected to 16S rRNA sequencing.Follow-up visits were conducted for individuals with HIV after 2years of combined antiretroviral therapy(cART),and they were grouped based on CD4~+T cell counts.Differential and correlation analyses were performed using R software.Results A total of 43 males infected with HIV and 15 healthy controls(HC)were included.Among the individuals with HIV,9 were classified into the immunological non-responder(INR)group,9 into the intermediate(M)group,and 25 into the immunological responder(IR)group,based on CD4~+T cell counts after 2 years of cART.No significant differences were observed in age among the four groups(P=0.556).Diversity analysis of saliva samples showed statistically significant differences inβ-diversity among the INR,M,IR,and HC groups(P=0.003),with increased microbial richness in the IR group.At the genus level,the top five dominant genera distribution differed between the INR,IR,and HC groups.The enrichment of Treponema_2 and Aggregatibacter genera in the IR group was positively correlated with increased CD4~+T cell counts and CD4/CD8 cell ratios.In contrast,enrichment of the Solobacterium genus in the INR group was negatively correlated with increased CD4~+T cell counts.Receiver operating characteristic curve analysis demonstrated that Treponema_2 had high accuracy in distinguishing between the INR and IR states.Conclusions Significant differences in the baseline oral microbiota were observed among individuals with HIV and different immune reconstitution statuses.Specific characteristics of oral microbiota and marker genera(such as Treponema_2)may play important roles in immune reconstitution in individuals infected with HIV.