Biological Sciences Division
Published July 23, 2024 | Version v1
Journal article Open

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

Creators

  • 1. University of Minnesota
  • 2. University of Oklahoma
  • 3. Harvard University
  • 4. University of Chicago

Description

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.

Data availability

Milk RNA and DNA sequencing data have been deposited in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) under study accession phs003408.v1.p1 [https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003408.v1.p1]. Raw sequencing data are available under controlled access in compliance with the study IRB. Use of the data is limited to health/medical/biomedical purposes, including methods development and excluding the study of population origins. Data access is provided by dbGaP (https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=login) for certified investigators and does not require local IRB approval. Milk and infant fecal metagenomic sequencing data are available at SRA accession PRJNA1019702. Raw metabolomics data is available at Metabolights accession MTBLS10138. Milk metabolite abundances, gene expression matrices, and microbial abundance tables are available in Supplementary Data 14.

The code to reproduce the analyses and figures in this manuscript is available at https://github.com/kelsj/CMV_milk_genomics (https://doi.org/10.5281/zenodo.11224392).

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Additional details

Identifiers

DOI
10.1038/s41467-024-50282-4
Other
oai:uchicago.tind.io:13004

Funding

Department of Pediatrics, University of Minnesota
Masonic Cross-Departmental Research Grant
University of Minnesota
Masonic Children’s Hospital Research Fund Award
NIH/NICHD
R01HD109830
NIH/NICHD
R01HD099866
NIH/NICHD
R21HD099473
NIH/NICHD
F32HD105364
NIH/NIDCR
T90DE0227232
Office of Academic and Clinical Affairs, University of Minnesota
Faculty Research Development Grant
Presbyterian Health Foundation
Team Science Award

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Genetics, Genomics, and Systems Biology, Medicine, Molecular Metabolism and Nutrition