Blocking CMV transmission through the human milk microbiome and metabolome

  • Marquez-Lago, Tatiana (Primary Chief Investigator (PCI))
  • Song, Jiangning (Chief Investigator (CI))
  • Leier, André (Chief Investigator (CI))

Project: Research

Project Details

Project Description

Cytomegalovirus (CMV) is a frequent cause of tissue-invasive disease in immunocompromised individuals and infants, the most frequent cause of congenital infection, and a major non-genetic cause of hearing loss and neurologic disabilities in children. There is a fast-growing list of complications to CMV, and associations to chronic and life-threatening illnesses, urging efforts to better understand CMV transmission dynamics. Among CMV transmission modes, human milk (HM) has been recognized to have the largest global impact on population prevalence. Notably, over 90% of CMV seropositive women shed virus in HM, and about 50% of infants exposed to CMV in HM become infected by six months of age, despite passive immunization by antiviral antibodies acquired transplacentally and through the HM of seropositive mothers. Factors determining this seeming stochastic CMV transmission remain largely unknown. However, it is known that metabolites, such as human milk oligosaccharides (HMOs), feed human microbiota and can also act as soluble decoy receptors, blocking the attachment of viral pathogens to epithelial cells. It is also known that commensal microbiota density and diversity impact sensitivity to viral infections by directly competing with pathogens for colonization sites and resources, and interacting with and developing the infant immune system.
This proposal’s objective is to systematically and quantitatively study the role and interactions of the HM metabolome and microbiome in CMV transmission. Our solid preliminary data already show that CMV seronegative and seropositive mothers have distinct HM microbiome and metabolome profiles, and that there are clear functional differences among HM microbiome-metabolome ecologies of three seropositive groups, namely that of seropositive mothers non-shedding (NS), shedding but not transmitting (SNT), and shedding and transmitting (ST). Our long-term goal is to elucidate key microbiome-metabolome combinations inhibiting viral transmissions via HM, and to bioengineer milk formula and HM supplements, in a personalized manner. Our central hypothesis is that certain combinations of HM microbiota and metabolites prevent CMV transmissions, and that these combinations vary among individual dyads, but follow traceable and reproducible patterns. Completion of the work proposed here will ultimately allow the design of precision interventions.
StatusActive
Effective start/end date1/04/2131/03/25