Maternal HIV infection and the milk microbiome.

ABSTRACT

BACKGROUND: 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. RESULTS: 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 (R2 = 0.006, p = 0.041), region/country (R2 = 0.014, p = 0.007), and duration of lactation (R2 = 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 (R2 = 0.003, p = 0.896), by combination antiretroviral therapy (R2 = 0.0009, p = 0.909), by advanced maternal disease (R2 = 0.003, p = 0.263), or in cases of infant infection either through isolated early mucosal (R2 = 0.003, p = 0.197) or early mucosal and breast milk transmission (R2 = 0.002, p = 0.587). CONCLUSIONS: 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.