A mother’s unintentional gift at birth

C-section rates are increasing world-wide. In a recent study, we have found that specific bacteria from the mother’s gut are not only passed on to the newborn but also more strongly stimulate the baby’s immune responses early on in case of vaginal birth but not after C-section.
A mother’s unintentional gift at birth

In our new paper published recently in Nature Communications https://www.nature.com/articles/s41467-018-07631-x, we have found that a mother transfers specific gut bacteria to her newborn during vaginal delivery. These transferred strains carry important functions that are linked to an increased potential to stimulate the baby’s immune system during the very first days of life. While these findings are already interesting, we have also found that this mother-to-baby transfer of bacteria is impeded in the case of C-section, thus resulting in a strongly diminished stimulation of the immune system. Considering the fact that C-section born infants have a statistically higher risk of developing chronic diseases, these new findings may link earliest disturbances of gut microbiome colonization to immune priming deficiencies. This in turn opens up new perspectives for future neonatal research studies, making the field of neonatal microbiome research an exciting and fast growing domain!

Figure 1: Besides giving endless love and the miracle of life, a mother unknowingly also transfers her own bacteria to the newborn during vaginal delivery.

In 2014, I decided to resolve the mysteries surrounding the very early colonization of neonates by microbes together with Carine de Beaufort, paediatric endocrinologist at the main hospital in Luxembourg. Although much descriptive work had been done on the infant gut microbiome, the resolution was simply not high enough to be able to resolve what happens precisely during the first days of life. Therefore, we were highly motivated to study the earliest gut microbiome in unprecedented detail using high-resolution metagenomics data.

Figure 2: The Luxembourg-based Cosmic study is a joint project between the Luxembourg Centre for Systems Biomedicine (University of Luxembourg), the main hospital in Luxembourg (Centre Hospitalier de Luxembourg) and the Integrated BioBank of Luxembourg and involves collaborators in Sweden. The presented study was financed by the National Research Fund of Luxembourg, the Integrated BioBank of Luxembourg and the private foundation André et Henriette Losch.

In this new study, we not only developed and applied new in vitro and in silico methods to eliminate any potential impact of artifacts (which is unfortunately still largely under-estimated to date) but also validated important metagenomics-based findings in wet lab assays. While the gut microbiome structures and functions of neonates differed significantly according to delivery mode, individual-specific strains carrying these exact functions were identified in both mothers and vaginally delivered babies, but they were generally absent in the neonatal gut in the case of C-section delivery.  

Importantly, the gut microbiome of vaginally delivered neonates exhibited a significantly higher potential to synthesize lipopolysaccharide (LPS), which is highly immunogenic. Based on these findings, my team isolated LPS directly from neonatal stool samples and tested the effects in vitro. Thus, we were able to show that the early gut microbiome of vaginally delivered neonates harbors a considerably higher potential to stimulate the immune system, whereas the gut microbiome of C-section delivered babies did not. Furthermore, additional cytokine measurements in neonatal plasma samples showed a stronger activation of the immune system in case of vaginal delivery.

Figure 3: Summary of the study’s main findings.

This study provided us with fundamental insights into how the earliest gut microbiome that we receive from our own mother may influence each one of us from the first day of life onward. In this sense, we are very excited to see what clinical research may now come up with in order to help restore gut strain transfer and microbiome-associated immune stimulation in C-section delivered neonates. As C-section rates are globally increasing at alarming rates, Luxembourg with a C-section rate of currently 31% is not an exception. New interventions aimed at restoring an early ‘natural’ immune stimulation are therefore an important area for future development.