Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV

Abstract

Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of <250 and 30 women with CD4 of >500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included. We found that breast milk bacterial microbiomes in this study population were highly diverse but shared a core community composed of the Streptococcaceae, Staphylococcaceae, Moraxellaceae, and Eubacteriaceae families. The breast milk virome was dominated by human cytomegalovirus (CMV) and included the bacteriophage families Myoviridae, Siphoviridae, and Podoviridae. Bacterial microbiome and virome profiles and diversity were not significantly altered by HIV immunosuppression, as defined by a CD4 of <250. CMV viral load was not associated with maternal CD4 counts or infant mortality. In conclusion, we show that the core bacterial and viral communities are resilient in breast milk despite immunosuppression in WLHIV. IMPORTANCE Breastfeeding plays an important role in seeding the infant gut microbiome and mammary health. Although most studies focus on the diverse breast milk bacterial communities, little is known about the viral communities harbored in breast milk. We performed the first breast milk virome study of an HIV population. In this study cohort of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that breast milk harbors a core bacterial microbiome and a virome dominated by human cytomegalovirus. The virome and bacterial microbiome were not substantially altered by immunosuppression or associated with infant mortality. Together, these findings indicate resilience of the microbial community in breast milk compartmentalization. These findings advance out fundamental understanding of the breast milk core microbiome and virome interactions in the context of HIV disease.

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

“…Previous studies have characterized the breast milk bacterial microbiome and found a core microbiome in breast milk from women across geographic regions including Kenya, Spain, and the United States, among others ( 5 – 7 ). Staphylococcaceae and Streptococcaceae are the most abundant and prominent bacterial families found in breast milk universally.…”

“…Previous studies have shown that among WLHIV who are not on ART, the core breast milk bacterial microbiome is similar to that of HIV-negative women ( 5 , 6 , 15 ), and that immunosuppression does not appear to have a substantial impact on either breast milk DNA virome or bacterial microbiome ( 5 ). However, data is lacking on the impact of ART on the breast milk bacterial microbiome.…”

Human Milk Virome Analysis: Changing Pattern Regarding Mode of Delivery, Birth Weight, and Lactational Stage

“…The influence of lifestyle, maternal diet, and environment on the composition of the HM microbiota has been suggested [ 2 , 8 ]. Recently, Maqsood et al [ 30 ] found that cytomegalovirus (found in 98% of human milk samples) dominated the HM virome of HIV-positive mothers in Kenya, with the bacteriophage families Myoviridae , Siphoviridae , and Podoviridae ; virome profiles and diversity were not substantially altered by HIV immunosuppression or associated with infant mortality.…”

“…The exact origin of the HM virome remains unclear. The bacterial content might be generated from the maternal skin microbiota, entero-mammary pathway, commensal microbiota inhabiting human breast tissue, or the infant’s oral cavity, whereas the origin of the viral content remains unknown [ 30 ]. Regardless of the sources of the microbiome composition, infants received these microbial communities regularly during breastfeeding.…”

Breast Milk: A Meal Worth Having

“…Evidence suggest that the mother-to-infant virome transmission occurs, as BM and stool viromes from mother-infant pairs shared a significant homology of bacteriophages (135,136). Recent research on the role of immunosuppression on the bacteriome and virome of breast milk in HIV-positive women discovered that bacterial and viral communities are resilient in breast milk despite immunosuppression (137). There is a definite need for more longitudinal paired mother-infant studies designed to capture the dynamic nature of the milk and infant virome.…”