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

Author:

Johnson Kelsey E.ORCID,Hernandez-Alvarado Nelmary,Blackstad Mark,Heisel Timothy,Allert Mattea,Fields David A.,Isganaitis Elvira,Jacobs Katherine M.,Knights Dan,Lock Eric F.,Rudolph Michael C.ORCID,Gale Cheryl A.ORCID,Schleiss Mark R.ORCID,Albert Frank W.,Demerath Ellen W.,Blekhman Ran

Abstract

AbstractHuman 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.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Publisher

Springer Science and Business Media LLC

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