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Study Suggests Informative Microbial Communities Present in Placenta Tissue

NEW YORK (GenomeWeb) – The healthy human placenta is home to microbial communities that are largely distinct from those found at other body sites, according to a study appearing online today in Science Translational Medicine.

A Baylor College of Medicine team used a combination of 16S ribosomal RNA gene sequencing and metagenomic sequencing to look at the microbes and microbial genes present in placental samples from 320 individuals.

When they analyzed the microbial communities and compared them to microbiomes from various body sites in non-pregnant people, the researchers determined that placental communities differ from those at other body sites, but somewhat resemble the human mouth microbiome.

"We weren't expecting that [similarity to the mouth microbiome]. But in thinking about it, it made a lot of sense," the study's first author Kjersti Aagaard, an obstetrics, gynecology, and molecular biology researcher at the Baylor College of Medicine, told GenomeWeb Daily News.

"We've known for many years that women with a history of periodontal disease have an increased risk of preterm birth," she noted, pointing to other possible ties between the oral microbiome and pregnancy-related processes.

The new study suggests the placental microbiome is prone to containing commensal and non-pathogenic microbes from five phyla. But the team also saw subtle shifts in the gene content of microbiomes from placentas collected at preterm births. Likewise, representation by certain microbial taxonomical groups differed somewhat in placental samples from women who had experienced infections early in their pregnancies.

In another study published in Nature Communications this week, some members of the same group demonstrated that a high-fat maternal diet in mice during pregnancy and nursing can alter gut microbial communities in offspring after birth, even if mouse mothers-to-be are not obese.

Together, the studies argue against the notion that an individual's microbiome starts developing at the time of birth. Rather, prenatal factors seem to contribute to this process as well, explained Aagaard, senior author on the Nature Communications paper.

"It's really a complex array of interactions that go into establishing an infant's microbiome," she said.

There had been a few prior hints that some features of human microbial communities were influenced by events before birth, the researchers noted. For example, past studies have found somewhat distinct gut microbial communities in low birth weight infants born early compared to their full-term counterparts, suggesting some microbiome features might depend on time spent in the womb.

But despite prior evidence of bacteria in placental tissue samples, there has been some debate over whether healthy human placentas harbored microbes at all.

"For a long time we considered the placenta to be sterile," Aagaard explained, noting that that view began to change with the release of a recent microscopic study revealing bacterial cells in a subset of placental samples from uninfected women.

To look at this in more detail, the researchers used Roche 454 Titanium and Illumina HiSeq 2500 instruments to do 16S rRNA gene sequencing and metagenomic sequencing, respectively, on placental samples obtained in a sterile manner from 320 women.

The group included healthy women as well as women who had experienced pregnancy complications or infections (including urinary tract infections or sexually transmitted infections) during the early stages of pregnancy.

Indeed, sequence data from the placental samples confirmed that microbes reside in healthy human placentas. While not present at high abundance, Aagaard explained, the

Next, the researchers compared the placental microbe sequences with those found at skin, mouth, nose, vaginal, and gut sites tested by members of the Human Microbiome Project. The head-to-head analysis suggested placental microbiomes contained collections of microbes not generally found together at the other body sites, though the microbiomes were most similar to microbiomes described in the human oral cavity.

Generally speaking, the microbes found in the placenta were non-pathogenic — and potentially beneficial — bugs from a handful of phyla: Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria.

But the team also saw subtle taxonomic-level differences in placental microbiomes from individuals who had experienced urinary tract infections or other types of infection at early stages of pregnancy.

There were also apparent differences in the bacterial pathways present in placentas from women who gave birth early or at term. In the preterm placentas, for example, the team saw a jump in genes used to produce compounds known as isoquinoline alkaloids. On the other hand, the placentas collected from full-term births were more likely to contain microbial genes contributing to biotin metabolism.

"We've known for many years that infants born prematurely have low levels of biotin," Aagaard said. "We've always assumed this has to do with the infants' biotin metabolism, but it actually may be a reflection of how that infant's microbiome was populated — potentially from the placenta."

She and her colleagues have already started on a longitudinal study of more than 500 pregnant women deemed to be at risk of preterm birth. For that effort, researchers will track microbiome patterns across pregnancy using samples from several, non-placental body sites, including the mouth microbiome, which they now believe may provide clues about microbes present in the placenta.