Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, 10833 Le Conte Ave., 22-340 MDCC, Los Angeles, CA, 90095, USA.
The Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Microbiome. 2024 Sep 28;12(1):182. doi: 10.1186/s40168-024-01843-8.
Children born to women with HIV but who do not become HIV infected experience increased morbidity and mortality compared with children born to women without HIV. The basis of this increased vulnerability is unknown. The microbiome, specifically the infant gut microbiome, likely plays an important role in infant immune development. The human milk microbiome is thought to have an important role in the development of the infant gut and therefore, if perturbed, may contribute to this increased vulnerability. We investigated the effects of HIV and its therapies on the milk microbiome and possible changes in the milk microbiome before or after infant HIV infection.
Seven-hundred fifty-six human milk samples were selected from three separate studies conducted over a 15-year period to investigate the role of HIV and its therapies on the human milk microbiome. Our data reveal that the milk microbiome is modulated by parity (R = 0.006, p = 0.041), region/country (R = 0.014, p = 0.007), and duration of lactation (R = 0.027-0.038, all p < 0.001). There is no evidence, however, using 16S rRNA V4 amplicon sequencing, that the human milk microbiome is altered by HIV infection (R = 0.003, p = 0.896), by combination antiretroviral therapy (R = 0.0009, p = 0.909), by advanced maternal disease (R = 0.003, p = 0.263), or in cases of infant infection either through isolated early mucosal (R = 0.003, p = 0.197) or early mucosal and breast milk transmission (R = 0.002, p = 0.587).
The milk microbiome varies by stage of lactation, by parity, and by region; however, we found no evidence that the human milk microbiome is altered by maternal HIV infection, disease severity, or antiretroviral therapy. Additionally, we found no association between the milk microbiome and transmission of HIV to the infant. Investigations including higher resolution microbiome approaches or into other potential mechanisms to understand why the approximately one million children born annually to women with HIV escape infection, but do not escape harm, are urgently needed. Video Abstract.
与未感染 HIV 的女性所生的孩子相比，感染 HIV 的女性所生的孩子即使没有感染 HIV，其发病率和死亡率也会增加。这种脆弱性增加的基础尚不清楚。微生物组，特别是婴儿肠道微生物组，可能在婴儿免疫发育中发挥重要作用。人们认为人乳微生物组对婴儿肠道的发育有重要作用，因此，如果受到干扰，可能会导致这种脆弱性增加。我们研究了 HIV 及其疗法对母乳微生物组的影响，以及婴儿感染 HIV 前后母乳微生物组可能发生的变化。
从三个不同的研究中选择了 756 个人乳样本，这些研究是在过去 15 年中进行的，旨在研究 HIV 及其疗法对人乳微生物组的作用。我们的数据表明，母乳微生物组受产次（R=0.006，p=0.041）、地区/国家（R=0.014，p=0.007）和哺乳期长短（R=0.027-0.038，均 p<0.001）的影响。然而，使用 16S rRNA V4 扩增子测序，没有证据表明母乳微生物组受到 HIV 感染（R=0.003，p=0.896）、联合抗逆转录病毒治疗（R=0.0009，p=0.909）、产妇晚期疾病（R=0.003，p=0.263）或婴儿感染的影响，无论是通过孤立的早期黏膜（R=0.003，p=0.197）还是早期黏膜和母乳传播（R=0.002，p=0.587）。
母乳微生物组随泌乳期的不同而变化，随产次和地区的不同而变化；然而，我们没有发现证据表明母乳微生物组因产妇 HIV 感染、疾病严重程度或抗逆转录病毒治疗而发生改变。此外，我们没有发现母乳微生物组与 HIV 向婴儿传播之间的关联。迫切需要开展包括更高分辨率微生物组方法在内的研究，或开展其他潜在机制的研究，以了解为什么每年约有 100 万名感染 HIV 的女性所生的孩子没有感染 HIV，但却没有逃脱伤害。
