Longitudinal comparison of the developing gut virome in infants and their mothers

Walters, William A.; Granados, Andrea; Ley, Catherine; Federman, Scot; Stryke, Doug; Santos, Yale A.; Haggerty, Thomas D.; Sotomayor-González, Alicia; Servellita, Venice; Ley, Ruth E.; Parsonnet, Julie; Chiu, Charles Y.

doi:10.1016/j.chom.2023.01.003

Cited by 30 publications

(27 citation statements)

References 40 publications

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“…The reasons for the difference in bacteriophage colonization and function by delivery mode up to 24 months is still yet to be determined. While differential acquisition of the maternal virome is possible, as infants delivered by CS bypass the birth canal and maternal vaginal and perineal microbiome exposure, studies suggest that maternal to infant transmission of the virome in early life is already very low [14, 15]. It has been suggested dietary factors such as breastfeeding contribute to early life virome colonization, however there were no differences in breastfeeding by delivery mode in our study (Table S1).…”

Section: Resultsmentioning

confidence: 56%

Delivery mode impacts gut bacteriophage colonization during infancy

Subramanian,

Romero-Soto,

Stern

et al. 2023

Preprint

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BackgroundCesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory and immune health outcomes. Although gut bacteriophages can alter gut microbiome composition and impact host immune responses, little is known about how delivery mode impacts bacteriophage colonization over time. To begin to address this we examined how delivery mode affected bacteriophage colonization over the first two years of life.ResultsShotgun metagenomic sequencing was conducted on 272 serial stool samples from 55 infants, collected at 1-2 days of life and 2, 6, 12 and 24 months. 33/55 (60%) infants were born by vaginal delivery. DNA viruses were identified, and by host inference, 94% of the viral sequences were found to be bacteriophages. Alpha diversity of the virome was increased in vaginally delivered infants compared to cesarean section delivered infants at 2 months (Shannon index, p=0.022). Beta diversity significantly differed by delivery mode at 2, 6, and 12 months when stratified by peripartum antibiotic use (Bray–Curtis dissimilarity, all p<0.05). Significant differentially abundant predicted bacteriophage hosts by delivery mode were seen at all time points. Moreover, there were differences in predicted bacteriophage functional gene abundances up to 24 months by delivery mode. Many of the functions considered to play a role in host response were increased in vaginal delivery.ConclusionsClear differences in bacteriophage composition and function were seen by delivery mode over the first two years of life. Given that phages are known to affect host immune response, our results suggest that future investigation into how delivery mode may lead to adverse inflammatory outcomes should not only include bacterial microbial colonization but also the potential role of bacteriophages and transkingdom interactions.

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Section: Resultsmentioning

confidence: 56%

Delivery mode impacts gut bacteriophage colonization during infancy

Subramanian,

Romero-Soto,

Stern

et al. 2023

Preprint

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“…Other studies with older children (range 8 days -17 years) showed changes in the bacterial alpha and beta diversity as well as differentiating bacteria 16,51,53 . Since the early life microbiome maturation is a dynamic process that occurs over the rst 3-4 years of life to reach an adult-like pro le, we expect to see this difference in which the impact of SARS-CoV-2 in older children is more in line with ndings in adults 43,60 . A limitation of the study was the limited number of samples for SARS-CoV-2 positive samples for infants.…”

Section: Discussionmentioning

confidence: 93%

“…Previous studies have shown that adult and infant gut microbiomes differ substantially 27,[43][44][45][46] . Using linear mixed effects models (LME) and PERMANOVA to compare microbiome diversity, we found that maternal and infant samples had signi cantly different bacterial richness (p = 0.0002) and alpha diversity (p < 0.0001), but not beta diversity (PERMANOVA, p = 0.85).…”

Section: Dna Virome and Bacterial Microbiome Differences Between Moth...mentioning

confidence: 99%

Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants

Maqsood,

Holland,

et al. 2024

Preprint

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Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that while the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women’s positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). However, gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

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“…pathogen-mediated versus non-pathogen related), and therefore included these factors in our analyses. However, analyses such as this are inherently limited by natural variation among individuals ( 84-86 ), the relative compositions of virulent, lytic phage versus those with a temperate lifestyle, and existing limitations of viral taxonomic databases. Despite these caveats, we observe some striking results that suggest phages hold great promise as signatures of dysbiosis across systems.…”

Section: Discussionmentioning

confidence: 99%

Phage as signatures of healthy microbiomes

Wheatley,

Holtappels,

Koskella

2024

Preprint

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Parasites are foundational to ecosystem health both as indicator species of community productivity but also as drivers of diversity. In bacterial communities, bacteriophage viruses can play such a role as they track the dynamic composition of bacterial hosts, and in the case of lytic phages, confer a growth advantage to lower abundance bacteria while adapting to more common ones. We set out to test whether viromes can be used as signatures of microbiome health using previously published results across systems. By comparing observed phage and bacterial diversity between microbiomes characterized by disturbance (so-called dysbiosis) and those considered control populations, we were able to identify some key commonalities. While just under half of studies report significant changes in viral species richness in dysbiosis, just under two thirds of studies find the viral composition to shift in dysbiosis, with specific viral taxa enrichment acting as a common signature of dysbiosis. Our analyses also suggest that the positive relationship between bacteriome and virome alpha diversity observed in health breaks down under microbiome disturbance. Overall, while specific viral signatures of dysbiosis are likely to be highly disease- and condition-specific, existing ecological theory shows clear promise in predicting and explaining microbiome health. Future data on bacteria-phage diversity relationships may provide us with much needed opportunity to diagnose, treat, and better understand the causes of dysbiosis.

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Longitudinal comparison of the developing gut virome in infants and their mothers

Cited by 30 publications

References 40 publications

Delivery mode impacts gut bacteriophage colonization during infancy

Delivery mode impacts gut bacteriophage colonization during infancy

Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants

Phage as signatures of healthy microbiomes

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