Lewy Tyler, Hong Bo-Young, Weiser Barbara, Burger Harold, Tremain Andrew, Weinstock George, Anastos Kathryn, George Michael D
1 Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California.
2 The Jackson Laboratory, Farmington, Connecticut.
AIDS Res Hum Retroviruses. 2019 Mar;35(3):276-286. doi: 10.1089/AID.2017.0200. Epub 2018 Jul 23.
Human immunodeficiency virus (HIV)-associated nonacquired immunodeficiency syndrome (AIDS) conditions, such as cardiovascular disease, diabetes, osteoporosis, and dementia are more prevalent in older than in young adult HIV-infected subjects. Although the oral microbiome has been studied as a window into pathogenesis in aging populations, its relationship to HIV disease progression, opportunistic infections, and HIV-associated non-AIDS conditions is not well understood. We utilized 16S rDNA-based pyrosequencing to compare the salivary microbiome in three groups: (1) Chronically HIV-infected women >50 years of age (aging); (2) HIV-infected women <35 years of age (young adult); and (3) HIV-uninfected age-matched women. We also examined correlations between salivary dysbiosis, plasma HIV RNA, CD4 T cell depletion, and opportunistic oral infections. In both aging and young adult women, HIV infection was associated with salivary dysbiosis characterized by increased abundance of Prevotella melaninogenica and Rothia mucilaginosa. Aging was associated with increased bacterial diversity in both uninfected and HIV-infected women. In HIV-infected women with oral coinfections, aging was also associated with reduced abundance of the common commensal Veillonella parvula. Patients taking antiretroviral therapy showed increased numbers of Neisseria and Haemophilus. High plasma HIV RNA levels correlated positively with the presence of Prevotella and Veillonella, and negatively with the abundance of potentially beneficial Streptococcus and Lactobacillus. Circulating CD4 T cell numbers correlated positively with the abundance of Streptococcus and Lactobacillus. Our findings extend previous studies of the role of the microbiome in HIV pathogenesis, providing new evidence that HIV infection is associated with a shift toward an increased pathogenic footprint of the salivary microbiome. Taken together, the data suggest a complex relationship, worthy of additional study, between chronic dysbiosis in the oral cavity, aging, viral burden, CD4 T cell depletion, and long-term antiretroviral therapy.
人类免疫缺陷病毒（HIV）相关的非获得性免疫缺陷综合征（AIDS）疾病，如心血管疾病、糖尿病、骨质疏松症和痴呆症，在老年HIV感染受试者中比在年轻成人中更为普遍。尽管口腔微生物群已被作为了解老年人群发病机制的一个窗口进行研究，但其与HIV疾病进展、机会性感染及HIV相关非AIDS疾病的关系尚未完全明确。我们利用基于16S rDNA的焦磷酸测序技术比较了三组人群的唾液微生物群：（1）年龄大于50岁的慢性HIV感染女性（老年组）；（2）年龄小于35岁的HIV感染女性（年轻成人组）；以及（3）未感染HIV的年龄匹配女性。我们还研究了唾液生态失调、血浆HIV RNA、CD4 T细胞耗竭和机会性口腔感染之间的相关性。在老年和年轻成人女性中，HIV感染均与唾液生态失调有关，其特征为产黑素普雷沃菌和黏液罗氏菌丰度增加。在未感染和HIV感染的女性中，衰老均与细菌多样性增加有关。在合并口腔感染的HIV感染女性中，衰老还与常见共生菌小韦荣球菌丰度降低有关。接受抗逆转录病毒治疗的患者中奈瑟菌属和嗜血杆菌属数量增加。血浆HIV RNA水平高与普雷沃菌属和韦荣球菌属的存在呈正相关，与潜在有益菌链球菌属和乳杆菌属的丰度呈负相关。循环CD4 T细胞数量与链球菌属和乳杆菌属的丰度呈正相关。我们的研究结果扩展了先前关于微生物群在HIV发病机制中作用的研究，提供了新的证据表明HIV感染与唾液微生物群致病足迹增加有关。综上所述，这些数据表明口腔慢性生态失调、衰老、病毒载量、CD4 T细胞耗竭和长期抗逆转录病毒治疗之间存在复杂关系，值得进一步研究。
