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Identification of bacteriophage DNA in human umbilical cord blood
Jennifer A. Sequoia, … , Virginia D. Winn, Paul L. Bollyky
Jennifer A. Sequoia, … , Virginia D. Winn, Paul L. Bollyky
Published July 8, 2025
Citation Information: JCI Insight. 2025;10(13):e183123. https://doi.org/10.1172/jci.insight.183123.
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Research Article Infectious disease Microbiology

Identification of bacteriophage DNA in human umbilical cord blood

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Abstract

Bacteriophages, viruses that parasitize bacteria, are abundant in the human microbiome and may influence human health, in part, through their interactions with bacterial hosts. Whether endogenous bacteriophages or their products are vertically transmitted from mother to fetus during human pregnancy is not known. Here, we searched for bacteriophage sequences from five bacteriophage databases (474,031 total sequences) in cell-free DNA (cfDNA) of paired maternal and umbilical cord blood samples from two independent cohorts. First, we sequenced cfDNA from 10 pairs of maternal and cord blood samples, including four pairs affected by preeclampsia. We validated our findings in a previously published dataset of 62 paired maternal and cord blood samples, including 43 pairs from preterm or chorioamnionitis-affected deliveries. We identified 94 and 596 bacteriophage sequences in maternal and cord blood cfDNA samples from the first and second cohort, respectively. We identified 58 phage sequences across maternal-infant dyads and 581 phage sequences that were unique to a single sample. We did not identify any phage sequences consistently associated with preeclampsia, preterm, or chorioamnionitis-affected samples. This study demonstrated the presence of bacteriophage DNA in human cord blood at birth, providing evidence that the human fetus is exposed to bacteriophage DNA in utero.

Authors

Jennifer A. Sequoia, Naomi L. Haddock, Paw Mar Gay, Layla J. Barkal, Purnima Narasimhan, Nadine Martinez, Virginia D. Winn, Paul L. Bollyky

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Figure 2

Bacteriophage DNA in umbilical cord blood in Witt dataset.

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Bacteriophage DNA in umbilical cord blood in Witt dataset.
(A) Descripti...
(A) Description of the cohort from the Witt dataset. (B) Bar graph with the number of phage sequences identified from each phage database among all Witt samples. (C) Bar graph of the number of phage sequences (red) present in each sample. (D) Bar graph of maternal-fetal pairs in which both samples contained phage sequences. Plot depicts the number of phage sequences identified only in maternal samples (red), only in fetal samples (blue), or in both samples from each pair (purple). Numbers above represent the number of phage sequences in each category. (E) Histogram depicting the number of samples in which each phage sequence was present. Red number indicates the number of phage sequences in each category. (F) Venn diagram depicting the overlap in the phage sequences identified in the POPE and Witt cohorts. C–F represent the combined results from the 5 phage databases.

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