Lactobacillus-depleted vaginal microbiota in HIV-infected pregnant women are associated with increased local inflammation and preterm birth. Lactobacillus-depleted vaginal microbiota in HIV-infected pregnant women

Background Pregnant women with HIV infection have an elevated risk of preterm birth of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of HIV-infected pregnant women in a UK population. Methods Prospective study of HIV-1 infected (n=53) and uninfected (n=22) pregnant women in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. The relationships between bacterial composition, inflammatory response, HIV status and gestational age at delivery were explored. Findings here was a high rate of preterm birth (PTB) among HIV infected women (12%). In the second trimester the vaginal microbiota was more diverse in HIV-1 infected than in uninfected women (Inverse Simpson Index, p=0.0004 and Species Observed, p=0.009). Pregnant women with HIV-1 infection had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15% vs 54%) than uninfected women and higher prevalence of L. iners dominant (VMB III, 36% vs 9% and VMB IIIB, 15% vs 5%) and mixed anaerobes (VMB IV, 21% vs 0%). VMB III/IIIB and IV were associated with PTB and with increased local inflammation (cervicovaginal fluid (CVF) cytokine concentrations in upper quartile). High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably Th1: IL-1b. Interpretation There is an association between local inflammation, vaginal dysbiosis and PTB in HIV infection. Understanding the potential of specific ART to influence this cascade will be important to improve birth outcomes in this population.

【研究背景】人类免疫缺陷病毒（HIV）感染孕妇发生早产的风险升高，但其病因尚未明确，且即使HIV得到成功抑制，该风险仍持续存在。HIV感染高风险女性存在共同的细菌谱特征，该特征与不良妊娠结局相关。本研究旨在探索英国人群中HIV感染孕妇分娩孕周的相关影响因素。
【研究方法】本研究为前瞻性研究，纳入53名HIV-1感染孕妇及22名未感染孕妇，分别采用宏分类组学（metataxonomics）与多重免疫分析法（multiplexed immunoassays）检测其阴道微生物群及宫颈阴道细胞因子微环境（cervicovaginal cytokine milieu）。本研究分析了细菌组成、炎症反应、HIV感染状态与分娩孕周之间的关联。
【研究结果】结果显示，HIV感染孕妇的早产（preterm birth, PTB）发生率较高，达12%。妊娠中期时，HIV-1感染孕妇的阴道微生物群多样性高于未感染孕妇（逆辛普森指数（Inverse Simpson Index）：p=0.0004；观测物种数（Species Observed）：p=0.009）。与未感染孕妇相比，HIV-1感染孕妇的卷曲乳杆菌（L. crispatus）主导型阴道微生物群（VMB I）检出率更低（15% vs 54%），而惰性乳杆菌（L. iners）主导型（VMB III：36% vs 9%；VMB IIIB：15% vs 5%）及混合厌氧菌型（VMB IV：21% vs 0%）的检出率更高。VMB III/IIIB及VMB IV型与早产及局部炎症水平升高相关（宫颈阴道液（cervicovaginal fluid, CVF）细胞因子浓度处于上四分位数区间）。高微生物多样性及厌氧菌丰度升高同样与CVF促炎细胞因子水平相关，其中尤以1型辅助T细胞（Th1）相关的白细胞介素1β（IL-1β）最为显著。
【研究解读】HIV感染状态下，局部炎症、阴道微生态失调与早产之间存在关联。明确特定抗反转录病毒治疗（Antiretroviral Therapy, ART）对这一病理级联反应的调控潜力，对于改善该人群的妊娠结局具有重要意义。