Human cytomegalovirus in breast milk is associated with milk composition and the infant gut microbiome and growth

Kelsey E. Johnson (), Nelmary Hernandez-Alvarado, Mark Blackstad, Timothy Heisel, Mattea Allert, David A. Fields, Elvira Isganaitis, Katherine M. Jacobs, Dan Knights, Eric F. Lock, Michael C. Rudolph, Cheryl A. Gale, Mark R. Schleiss, Frank W. Albert, Ellen W. Demerath and Ran Blekhman
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Kelsey E. Johnson: University of Minnesota
Nelmary Hernandez-Alvarado: University of Minnesota Medical School
Mark Blackstad: University of Minnesota Medical School
Timothy Heisel: University of Minnesota Medical School
Mattea Allert: University of Minnesota
David A. Fields: University of Oklahoma Health Sciences Center
Elvira Isganaitis: Harvard Medical School
Katherine M. Jacobs: University of Minnesota Medical School
Dan Knights: University of Minnesota
Eric F. Lock: University of Minnesota School of Public Health
Michael C. Rudolph: Oklahoma University Health Sciences Center
Cheryl A. Gale: University of Minnesota Medical School
Mark R. Schleiss: University of Minnesota Medical School
Frank W. Albert: University of Minnesota
Ellen W. Demerath: University of Minnesota School of Public Health
Ran Blekhman: University of Chicago

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full-term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate two opposing CMV-associated effects on infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full-term infant development.

Date: 2024
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DOI: 10.1038/s41467-024-50282-4

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