Lack of detection of a human placenta microbiome in samples from preterm and term deliveries
Published in Microbiology
Historically, it was believed that the contents of the gravid uterus (placenta, amniotic cavity, and fetus) are sterile, known as the “sterile womb hypothesis”. However, recent studies have proposed that the womb is not sterile and is instead inhabited by a distinct, commensal microbiome. These studies use modern DNA deep sequencing techniques to detect a low microbial biomass community. However, these studies often have a notable lack of sequenced matched samples (e.g. maternal saliva or vaginal samples) and thorough negative controls, which are crucial to differentiate between authentic organisms and reagent contamination. Our group performed 16S rRNA gene qPCR, 16S marker sequencing, and shotgun metagenomic sequencing on placenta samples from term and preterm deliveries alongside matched samples and negative controls to see if we could detect a placental microbiome.
With the help of the PennCHOP Microbiome Program, the Maternal and Child Health Research Center at UPenn, and March of Dimes, we analyzed samples from 20 term and 20 preterm pregnancies, including saliva, vaginal swabs, and maternal and fetal side placental biopsies. The qPCR data showed that the placenta samples had low bacterial abundance indistinguishable from the background seen in the negative control samples, unlike the high abundance seen in saliva and vaginal samples. In our 16S sequencing data, the placenta samples did initially show a low level of bacterial DNA—however, we found that a majority of the bacterial lineages seen in placenta were also found in our negative controls and are documented contaminants. Performing cluster analysis showed that the communities seen in the placenta samples were not different from those in the negative control samples. Shotgun metagenomics allowed us to deep sequence these samples for all of the DNA present. After filtering out the human reads present, we saw that the majority of the remaining sequences from the placenta samples were annotated as Ralstonia, a known reagent contaminant and also seen in the negative controls. After further investigation, the remaining placenta reads could be attributed to erroneous classifications. In conclusion, our group did not detect an microbiome in placenta samples are term or preterm deliveries.
While the experimental data from this study showed negative results, the experimental design and execution demonstrated the importance of including thorough negative controls—specifically in low biomass microbiome studies. With the advent of intensive DNA sequencing methods and their widespread use in microbiome studies, it is important to understand the pitfalls of these techniques. Furthermore, the lack of detection of a microbiome in the placenta is also an important contribution to the fields of obstetrics and gynecology. The microbiome plays an import role in human health, and understanding its relevance during pregnancy and fetal development is an important aspect of this field. Recent studies suggesting to have found a microbiome inside the womb have opened a new line of thought about bacterial colonization of humans. With reports supporting both sides of the “sterile womb hypothesis”, it is important that we have thorough scientific investigations that generate reproducible results before moving forward with further research. This study underscores the importance of incorporating rigorous controls in the detection of an intrauterine microbiome.
Full paper can be found here: https://doi.org/10.1186/s40168-018-0575-4
Artwork done by Arwa Abbas
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Harnessing plant microbiomes to improve performance and mechanistic understanding
This is a Cross-Journal Collection with Microbiome, Environmental Microbiome, npj Science of Plants, and npj Biofilms and Microbiomes. Please click here to see the collection page for npj Science of Plants and npj Biofilms and Microbiomes.
Modern agriculture needs to sustainably increase crop productivity while preserving ecosystem health. As soil degradation, climate variability, and diminishing input efficiency continue to threaten agricultural outputs, there is a pressing need to enhance plant performance through ecologically-sound strategies. In this context, plant-associated microbiomes represent a powerful, yet underexploited, resource to improve plant vigor, nutrient acquisition, stress resilience, and overall productivity.
The plant microbiome—comprising bacteria, fungi, and other microorganisms inhabiting the rhizosphere, endosphere, and phyllosphere—plays a fundamental role in shaping plant physiology and development. Increasing evidence demonstrates that beneficial microbes mediate key processes such as nutrient solubilization and uptake, hormonal regulation, photosynthetic efficiency, and systemic resistance to (a)biotic stresses. However, to fully harness these capabilities, a mechanistic understanding of the molecular dialogues and functional traits underpinning plant-microbe interactions is essential.
Recent advances in multi-omics technologies, synthetic biology, and high-throughput functional screening have accelerated our ability to dissect these interactions at molecular, cellular, and system levels. Yet, significant challenges remain in translating these mechanistic insights into robust microbiome-based applications for agriculture. Core knowledge gaps include identifying microbial functions that are conserved across environments and hosts, understanding the signaling networks and metabolic exchanges between partners, and predicting microbiome assembly and stability under field conditions.
This Research Topic welcomes Original Research, Reviews, Perspectives, and Meta-analyses that delve into the functional and mechanistic basis of plant-microbiome interactions. We are particularly interested in contributions that integrate molecular microbiology, systems biology, plant physiology, and computational modeling to unravel the mechanisms by which microbial communities enhance plant performance and/or mechanisms employed by plant hosts to assemble beneficial microbiomes. Studies ranging from controlled experimental systems to applied field trials are encouraged, especially those aiming to bridge the gap between fundamental understanding and translational outcomes such as microbial consortia, engineered strains, or microbiome-informed management practices.
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Microbiome and Reproductive Health
Microbiome is calling for submissions to our Collection on Microbiome and Reproductive Health.
Our understanding of the intricate relationship between the microbiome and reproductive health holds profound translational implications for fertility, pregnancy, and reproductive disorders. To truly advance this field, it is essential to move beyond descriptive and associative studies and focus on mechanistic research that uncovers the functional underpinnings of the host–microbiome interface. Such studies can reveal how microbial communities influence reproductive physiology, including hormonal regulation, immune responses, and overall reproductive health.
Recent advances have highlighted the role of specific bacterial populations in both male and female fertility, as well as their impact on pregnancy outcomes. For example, the vaginal microbiome has been linked to preterm birth, while emerging evidence suggests that gut microbiota may modulate reproductive hormone levels. These insights underscore the need for research that explores how and why these microbial influences occur.
Looking ahead, the potential for breakthroughs is immense. Mechanistic studies have the power to drive the development of microbiome-based therapies that address infertility, improve pregnancy outcomes, and reduce the risk of reproductive diseases. Incorporating microbiome analysis into reproductive health assessments could transform clinical practice and, by deepening our understanding of host–microbiome mechanisms, lay the groundwork for personalized medicine in gynecology and obstetrics.
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