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肯尼亚 HIV 阳性产妇产后早期母乳微生物组的动态变化受抗生素影响,但不受抗逆转录病毒药物影响。

Dynamic Changes in Breast Milk Microbiome in the Early Postpartum Period of Kenyan Women Living with HIV Are Influenced by Antibiotics but Not Antiretrovirals.

机构信息

Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, Arizona, USA.

College of Health Solutions, Arizona State University, Tempe, Arizona, USA.

出版信息

Microbiol Spectr. 2022 Apr 27;10(2):e0208021. doi: 10.1128/spectrum.02080-21. Epub 2022 Apr 6.

Abstract

Shared bacteria between maternal breast milk and infant stool, infers that transfer of maternal breast milk microbiota through breastfeeding seeds the establishment of the infant gut microbiome. Whether combination antiretroviral therapy (cART) impacts the breast milk microbiota in women living with HIV is unknown. Since current standard of care for people living with HIV includes cART, it has been difficult to evaluate the impact of cART on the microbiome. Here, we performed a next-generation sequencing retrospective study from pre-ART era clinical trials in Nairobi, Kenya (between 2003-2006 before cART was standard of care) that tested the effects of ART regimens to prevent mother-to-child HIV transmission. Kenyan women living with HIV were randomized to receive either no ART during breastfeeding ( = 24) or cART (zidovudine, nevirapine, lamivudine;  = 25) postpartum. Using linear mixed-effects models, we found that alpha diversity and beta diversity of the breast milk bacterial microbiome changed significantly over time during the first 4 weeks postpartum (alpha diversity  < 0.0007; beta diversity  = 0.005). There was no statistically significant difference in diversity, richness, and composition of the bacterial microbiome between cART-exposed and cART-unexposed women. In contrast, antibiotic use influenced the change of beta diversity of the bacterial microbiome over time. Our results indicate that while early postpartum time predicts breast milk microbiome composition, cART does not substantially alter the breast milk microbiota in women living with HIV. Hence, cART has minimal impact on the breast milk microbiome compared to antibiotics use. Breastfeeding has important benefits for long-term infant health, particularly in establishing and shaping the infant gut microbiome. However, the impact of combination antiretroviral therapy exposure and antibiotics on the breast milk microbiome in women living with HIV is not known. Here, in a longitudinal retrospective study of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that antibiotic use significantly influenced breast milk microbiome beta diversity, but antiretrovirals exposure did not substantially alter the microbiome. Given the protective role of breastfeeding in maternal-infant health, these findings fill an important knowledge gap of the impact of combination antiretroviral therapy on the microbiome of women living with HIV.

摘要

母婴母乳和婴儿粪便之间共享的细菌表明,通过母乳喂养转移的母乳微生物群会在婴儿肠道微生物群的建立中播种。目前尚不清楚联合抗逆转录病毒疗法(cART)是否会影响艾滋病毒感染者的母乳微生物群。由于目前艾滋病毒感染者的标准护理包括 cART,因此很难评估 cART 对微生物组的影响。在这里,我们对肯尼亚内罗毕的前 ART 时代临床试验进行了下一代测序回顾性研究(在 cART 成为标准护理之前的 2003-2006 年期间),该研究测试了抗逆转录病毒方案预防母婴 HIV 传播的效果。感染艾滋病毒的肯尼亚妇女随机分配在哺乳期接受或不接受抗逆转录病毒治疗(分别为 24 例)或产后接受 cART(齐多夫定、奈韦拉平、拉米夫定;25 例)。使用线性混合效应模型,我们发现母乳细菌微生物组的 alpha 多样性和 beta 多样性在产后的前 4 周内随时间显著变化(alpha 多样性 < 0.0007;beta 多样性 = 0.005)。cART 暴露和未暴露妇女的细菌微生物组多样性、丰富度和组成无统计学差异。相比之下,抗生素的使用会影响细菌微生物组随时间的 beta 多样性变化。我们的结果表明,虽然产后早期时间预测母乳微生物组组成,但 cART 不会实质改变感染艾滋病毒妇女的母乳微生物群。因此,与抗生素的使用相比,cART 对母乳微生物组的影响很小。母乳喂养对婴儿长期健康有重要益处,尤其是在建立和塑造婴儿肠道微生物群方面。然而,尚不清楚联合抗逆转录病毒治疗暴露和抗生素对感染艾滋病毒妇女母乳微生物群的影响。在这里,我们对来自前抗逆转录病毒治疗时代的肯尼亚感染艾滋病毒妇女进行了一项纵向回顾性研究,我们发现抗生素的使用显著影响了母乳微生物组的 beta 多样性,但抗逆转录病毒药物的暴露并没有实质上改变微生物组。鉴于母乳喂养在母婴健康中的保护作用,这些发现填补了联合抗逆转录病毒治疗对感染艾滋病毒妇女微生物组影响的重要知识空白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/9045247/5679a802ea55/spectrum.02080-21-f001.jpg

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