Our microbiome plays a crucial role in our health. But when does our colonization with bacteria begin? While scientists have long assumed that the first contact with bacteria occurs at birth, more recent studies have suggested that microorganisms may also be present in the uterus and in the amniotic fluid. A new analysis contradicts this thesis. Accordingly, the apparent evidence of a fetal microbiome is due to contamination of the samples. Under normal circumstances, the uterus and amniotic fluid are sterile, as originally thought.
At the turn of the 19th and 20th centuries, the French pediatrician Henry Tissier investigated when in our lives we first come into contact with bacteria. His result: The first colonization takes place during birth, the environment inside the womb is sterile. This dogma lasted for more than a century. However, as of 2010, several studies were published that seemed to contradict this, thus sparking a scientific controversy. The studies indicated that in a healthy pregnancy, bacteria could also be present inside the uterus.
Analysis from different perspectives
An international research team led by Katherine Kennedy from McMaster University in Canada now contradicts the assumption that the uterus could not be sterile. “Our analysis indicates that the detected microbial signals are likely due to contamination during clinical procedures for obtaining fetal specimens or during DNA extraction and DNA sequencing,” the authors said.
For the analysis, 46 experts from various specialist areas, including reproductive biology, microbiome research, immunology and bioinformatics, examined the studies published to date. In addition, they made mechanistic considerations from the perspective of their respective fields of how the fetus might come into contact with microorganisms and what influence the different possibilities would have on the detectable microbiome. “By considering several explanatory angles, we conclude that the available evidence strongly supports the ‘sterile uterus’ hypothesis,” the authors summarize.
Contamination as a source of error
The bioinformatician Thomas Rattei from the University of Vienna, one of the co-authors of the analysis, explains: “The special problem with these microbiomes lies in the very small concentrations of the bacteria present. Therefore, species present in traces must also be reliably identified and differentiated from contamination.” This was not reliably the case in studies that indicated bacterial colonization within the uterus. For future research, it is therefore important to pay particular attention to avoiding contamination or recognizing it as such.
Furthermore, the team concludes that the existence of living and replicating microbial populations in healthy fetal tissue would be inconsistent with basic concepts of immunology and clinical microbiology. “We are aware that our position is at odds with dozens of publications citing evidence for microbial populations in the uterus, but we believe in the validity of our multi-pronged approach,” the authors said.
Focus research efforts
Kennedy and her colleagues hope that their contribution can help focus future research efforts on the early microbiome on promising aspects and conduct them according to internationally uniform, reliable standards. “Knowing that the fetus is in a sterile environment confirms that bacterial colonization occurs during birth and in the early postnatal period, which is where therapeutic research on modulation of the microbiome should focus,” says co-author Jens Walter from University College Cork in Ireland.
An interesting research question is, for example, which metabolic products transmitted through the uterus prepare the child’s immune system for later life in a world full of microbes. For clinical practice, it is also relevant to better understand the importance of initial colonization during birth – especially with regard to which methods in caesarean births can help to ensure that the newborn can benefit from the maternal microbiome even without passing through the birth canal.
Source: Katherine Kennedy (McMaster University, Hamilton, Ontario, Canada) et al., Nature, doi: 10.1038/s41586-022-05546-8