The microbiome has been an area of intense study. However, many fundamental questions remain unanswered. For example, when the microbiome first establishes itself in a human. More specifically, whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are colonized by bacteria.

Now, a large team of 46 experts from around the world evaluated the evidence for the presence of microbes in human fetuses. After analyzing recent studies that characterized microbial populations in human fetuses, the researchers concluded that any signals of a microbiome in fetuses were, in fact, contamination. In turn, they refuted claims that humans are colonized by bacteria before birth.

Their perspective, “Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies,” is published in Nature.

Previous studies have suggested the presence of microorganisms in prenatal intrauterine locations. Such claims that the human placenta and amniotic fluid are normally colonized by bacteria would, if true, have serious implications for clinical medicine and pediatrics and would undermine established principles in immunology and reproductive biology.

Jens Walter, PhD, assembled a trans-disciplinary team of 46 leading experts from around the world to evaluate the evidence for microbes in human fetuses. [UCC]
To examine these claims, Jens Walter, PhD, professor of microbiology at University College Cork, Ireland and principal investigator at APC Microbiome Ireland, assembled a trans-disciplinary team of experts. Their goal was to “evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology, and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms.”

Although there are dozens of reports in the literature, the group focused on four papers (published in Nature Microbiology, Nature Medicine, Cell, and JCI Insight) as they assessed the fetus more directly than the others. Three of the studies used samples collected after vaginally delivered, elective, second-trimester pregnancy terminations and the fourth used samples collected immediately at birth from breech C-section deliveries. To compare the studies, the team reanalyzed the microbial profiling data that was publicly available.

The team found the prior claims to be inaccurate, unanimously refuted the concept of a fetal microbiome, and concluded that the detection of microbiomes in fetal tissues was due to contamination of samples drawn from the womb. Contamination may have occurred during vaginal delivery, clinical procedures, or laboratory analysis.

In their perspective, the authors encourage researchers to focus their studies on the microbiomes of mothers and their newborn infants and on the microbial metabolites crossing the placenta which prepare the fetus for post-natal life in a microbial world.

“This consensus provides guidance for the field to move forward, to concentrate research efforts where they will be most effective,” noted Walter. “Knowing that the fetus is in a sterile environment, confirms that colonization by bacteria happens during birth and in early post-natal life, which is where therapeutic research on modulation of the microbiome should be focused.”

The authors also provide guidance on how scientists can avoid pitfalls of contamination in the analysis of other samples where microbes are expected to be absent or present at low levels, such as internal organs and tissues within the human body.