Were we born with a microbiome? Maybe, maybe not!

Although ‘bacteria may be the only culture some people have’, just like good manners, bacteria in our microbiome are also something we acquire over time in our life. To understand the role of microbiome (and its variations) in health and disease, we first need to understand when humans start forming their first microbiome. The presence of microbiota during birth has been a controversial topic for decades. It was forever assumed that the mother’s womb is a sterile environment and babies were born without any microbes, but then scientists found microbial DNA in placenta and amniotic fluid. Past studies using multiplex 16s rRNA sequencing made the researchers believe that we were born with our microbiota. These days with modern medical devices to sample microbiome during delivery, we can look at those studies with a little more critique.

One of such critiques comes from K.M. Kennedy and her colleagues. They collected the first feces (meconium) from newborns directly during elective cesarean section deliveries instead of sampling it hours or days after birth- where the samples generally come up positive for the presence of microbial DNA.

Preterm cesarean delivery ensured that no vertical transmission of microbiota could happen from a mother to her child as it happens with labor deliveries due to rupture of membranes. To check for the presence of bacteria in the fetal meconium, researchers used two types of assays: bacterial culture, and RNA sequencing. For the culture, they used 20 samples and incubated them for 120 hours. In 7 samples no bacterial growth was detected after 120 hours. On the other hand, 12 samples showed growth of the following: 8 both anaerobic and aerobic (with S. Epidermidis being most dominant and in 3 samples it grew in both conditions), 3 had only aerobic bacteria growth (S. Epidermidis and P. Acne) and one was only present in anaerobic conditions (S. Epidermidis). They performed sequencing with the same samples. Most of the bacteria they detected were also present in the negative controls that they obtained from exposing cotton swabs to air of the operating theatre and PCR hood, manifesting the result of inevitable contamination. By performing two PCR runs (30 and 40 cycles) some positive data was also lost, contributing to the contamination theory. An interesting factor was that Bacteroides and Staphylococcus were only detected in fetal meconium in 4 samples and only one Bacteroides continued to be positive after both PCR cycles and Staph had no consistency throughout those cycles. Another interesting factor was that even though Staph was detected in 4 samples with sequencing, only two of those samples had Staph positive cultures! Want to hear something even more fascinating? P. Acne was positive in the growth culture but was not detected in any of the samples during sequencing! With all this in mind, our researchers conclude that they could not distinct microbial signature in fetal meconium from the negative control.

While this research may bring us closer to finally resolving the issue of “who came first, microbiota or the birth?”, we still have a long way to get there. The theory that bacterial colonization happens during birth and that placental IgGs obtained from our mothers (via the placenta, before birth) shapes the outcome of our microbiota during and after birth, seems more plausible with the data from this study. Even though they discuss a highly possible hypothesis, they did not actually prove the absence of the bacteria in fetal meconium, as they mention themselves, it could be that their methods are not sensitive enough. Hopefully, better technologies will help solve the problem of ‘inevitable contamination’. Antibuddies are most certainly excited to see how this theory will be proven (or destroyed) in the future!

Source: Kennedy, K.M., Gerlach, M.J., Adam, T. et al. Fetal meconium does not have a detectable microbiota before birth. Nat Microbiol (2021). https://doi.org/10.1038/s41564-021-00904-0

Article author: Ines Poljak. Ines is a MSc student at University of Copenhangen and works on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.

Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.

Check out Antibuddies’ blog post “Were we born with a microbiome? Maybe, maybe not!”.

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