Abstract:

To investigate the impact of antiretroviral therapy （ART） on the composition of microbial flora in the blood of HIV-infected individuals. Blood samples were collected from 28 ART-treated HIV-infected patients （ART group） and 30 untreated HIV-infected patients （naive group）. Metagenomic sequencing was performed to analyze differences in the composition of blood microbial communities. After metagenomic sequencing，a total of 2 001 686 valid sequences were obtained. Taxonomic annotation identified microbial species at 9 phyla，17 classes，35 orders，55 families，84 genera， and 141 species levels. The richness （Chao1 index） and diversity （Simpson index and Shannon index） of the ART group were significantly higher than those of the naive group. Genera such as Xanthomonas， Lactobacillus， Stutzerimonas， Providencia， Arcobacter， Cutibacterium， Enterococcus， and Thermus were significantly enriched in the ART group， while Pseudomonas， Azospirillum， Escherichia， Acinetobacter， and Stenotrophomonas were significantly enriched in the naive group. Further linear discriminant analysis effect size （LEfSe） （LDA>4， P<0.05） revealed 6 significantly differential species in the ART group and 5 in the naive group. Overall， the richness and diversity of microbiota in the blood of HIV infected individuals significantly improved after treatment. There were significant differences in the dominant species of blood microbiota at the phylum and genus levels between treated and untreated HIV infected individuals， and ART treatment may reduce pathogenic bacteria in the blood. The research results can provide new insights into the interaction between blood microbiota and HIV progression. Specific microbial species can serve as potential indicators for evaluating the effectiveness of HIV treatment and provide a basis for diagnosis and treatment strategy development.

Key words: human immunodeficiency virus, antiretroviral therapy, metagenomics, blood microbiome

摘要：

研究抗逆转录病毒治疗(antiretroviral therapy，ART)对HIV感染者血液中微生物菌落组成的影响。收集28例ART治疗的HIV感染者（ART组）和30例未治疗的HIV感染者（naive组），利用宏基因测序分析血液微生物菌群的物种组成差异。宏基因测序后共获得2 001 686条有效序列，经物种注释获得9个门、17个纲、35个目、55个科、84个属和141个种水平的物种。ART组的丰富度（Chao1指数）和多样性（Simpson指数和Shannon指数）显著高于naive组。黄单胞菌属、有益杆菌属、施蒂泽氏单胞菌属、普罗威登斯菌属、另类弓形菌属、表皮杆状菌属、肠球菌属和栖热菌属在ART组显著富集，假单胞菌属、固氮螺菌属、埃希氏菌属、不动杆菌属、寡养单胞菌属在naive组显著富集。进一步线性判别效应量分析（linear discriminant analysis effect size，LEfSe）发现ART组有6个物种，而naive组有5个物种存在显著性差异。综上，治疗后HIV感染者的血液中菌群微生物丰富度和多样性显著改善，治疗与未治疗的HIV感染者血液微生物在门水平和属水平的优势物种存在较大差异，且ART治疗可能减少血液中致病性细菌。研究结果可为血液微生物群与HIV进展间的相互作用提供新的见解，特定的微生物物种可作为评价HIV治疗效果的潜在指标，并为诊断和制定治疗策略提供依据。

关键词: 人免疫缺陷病毒, 抗逆转录病毒治疗, 宏基因组, 血液微生物组