尽管肠道菌群变化和相关的血液微生物组在艾滋病毒（HIV）感染者中与疾病进展相关，但异常的血液微生物组如何影响炎症和免疫修复尚不完全清楚。为了解决这些问题，本研究招募了24名健康对照者（HCs）和91名HIV感染者，包括30名未接受治疗的个体（TNs），31名免疫学非响应者（INRs）和30名免疫学响应者（IRs）；随后，我们使用基因组学测序和Olink蛋白质组学技术分析了这些个体外周血样品中的血液微生物组，并确定了与炎症相关的蛋白质。结果显示，TNs的血液中的菌群转位增加。接受抗逆转录病毒治疗的IRs和INRs的菌群转位未恢复到正常水平。此外，与HCs相比，TNs、IRs和INRs中的牙龈拟杆菌显著增加。牙龈拟杆菌与CD4+ T细胞计数、CD4/CD8比值、潜伏相关肽转化生长因子-β1和肿瘤坏死因子相关激活诱导细胞因子（TRANCE）呈负相关，与HIV库存呈正相关。布氏多杆菌和苏云金芽胞杆菌在TNs、IRs和INRs中显著降低，与CD4+ T细胞计数、CD4/CD8比值呈正相关，与HIV库存大小和促炎因子呈负相关。我们确定了一些与抗逆转录病毒治疗后CD4+ T细胞恢复相关的微生物种类，如普雷沃特拉属CAG:5226、厚壁拟杆菌属CAG:251、短尾熊消化杆菌、厌氧杆菌广泛、普雷沃特拉属AM34-19LB和介质微生物科颜氏兽杆菌，它们与HIV库存大小和促炎蛋白呈正相关。另一组与促炎蛋白呈负相关的细菌有多伟多布氏杆菌、苏云金芽胞杆菌、弧菌嗜致致病菌和巴氏不动杆菌。总之，艾滋病毒感染者血液中的不同微生物与持久性炎症和免疫修复密切相关，这表明HIV感染者的血液微生物组也影响疾病进展。意义：尽管HIV感染者的肠道菌群多样性和组成发生了变化，但我们对HIV感染者血液菌群的特征及其与疾病进展的相关性仍知之甚少。在这里，我们提供了HIV感染者血液菌群多样性增加的证据，这可能是由于肠道菌群转位引起的。此外，我们确定了一组与免疫恢复不良相关的微生物，如牙龈拟杆菌、普雷沃特拉属CAG:5226、厚壁拟杆菌属CAG:251、短尾熊消化杆菌、厌氧杆菌广泛、普雷沃特拉属AM34-19LB和介质微生物科颜氏兽杆菌。这项工作为针对HIV感染的免疫恢复的血液菌群治疗策略提供了科学基础。

Although gut microbiota alteration and related blood microbe profiles in human immunodeficiency virus (HIV)-infected individuals are associated with the disease progression, how abnormal blood microbe profiles influence the inflammation and immune restoration are not fully understood. To address these issues, this study enrolled 24 healthy controls (HCs) and 91 HIV-infected individuals, including 30 treatment-naïve individuals (TNs), 31 immunological non-responders (INRs), and 30 immunological responders (IRs); subsequently, we analyzed blood microbe profiles using metagenomic sequencing and Olink proteomics technology, and identify inflammation-related proteins in peripheral blood samples of these individuals. The results showed increased translocation of microbes in the blood of TNs. This translocation did not return to normal level in either IRs or INRs who received antiretroviral therapy. In addition, Porphyromonas gingivalis significantly increased in TNs, IRs, and INRs compared to HCs. P. gingivalis was inversely associated with CD4+ T-cell counts, CD4/CD8 ratio, latency-associated peptide transforming growth factor-β1, and tumor necrosis factor-related activation-induced cytokine (TRANCE) and positively associated with HIV reservoirs. Burkholderia multivorans and Bacillus thuringiensis significantly decreased in TNs, IRs, and INRs compared to HCs and were positively associated with CD4+ T-cell counts and the CD4/CD8 ratio and negatively associated with HIV reservoir size and pro-inflammatory factors. We identified several species of microbes that were associated with CD4+ T-cell restoration on antiretroviral therapy, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius were positively associated with HIV reservoir size and pro-inflammatory proteins. Another group of bacteria, B. multivorans, B. thuringiensis, Vibrio vulnificus, and Acinetobacter baumannii, which were negatively associated and pro-inflammatory proteins. In conclusion, different microbes within blood of HIV-infected individuals were found to be closely associated with persistent inflammation and immune restoration, suggesting the blood microbe profiles of HIV-infected individuals also influence disease progression. IMPORTANCE The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.