Extremely premature infants are at an elevated risk for brain damage, and there may be potential targets for the early treatment of such damage through changing the gut bacteria of premature infants, a new study found. In the study, researchers found that in a sample size of 60 extremely premature infants, an overgrowth of the bacterial strain Klebsiella is associated with an increased presence of certain immune cells that are correlated with the development of neurological damage in premature babies.
 
This was accompanied by elevated levels of certain T cells and an increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectant compounds. Combined, the researchers said that abnormal development of what they refer to as the gut microbiota-immune-brain axis in extremely premature babies may drive or exacerbate brain injury, and could be a promising target for intervention strategies.
 
The gut-immune-brain axis refers to the way that the gut microbiome, immune system, and brain develop in a closely interrelated way. Bacteria in the gut cooperate with immune factors, which in turn are involved in monitoring gut microbes and developing appropriate responses to them. Additionally, the gut is in contact with the brain via the vagus nerve, and less directly through the nervous system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” David Seki, lead author of the study, said. “The microorganisms of the gut microbiome – which is a vital connection of hundreds of species of bacteria, fungi, viruses and other microbes – are in equilibrium in healthy people. However, especially in premature babies whose immune systems and gut microbiomes have not been able to develop fully, certain shifts which aren’t ideal for brain development are more likely to occur, Seki said.
 
“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” David Berry, microbiologist and head of the research group at the Center for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna, and operational director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna, said. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”
 
The researchers were able to identify the biomarkers, such as excessive Klebsiella growth and the associated elevated T-cell levels linked to exacerbated brain damage for the first time, Lukas Wisgrill, University of Vienna neonatologist said. “We are able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system, and the brain develop, and how they interact in this process.” The study monitored a total of 60 premature infants all of whom were born before 28 weeks gestation and weighing less than 1 kg, for several weeks or even months. Microbiomes and their associated biomarkers were evaluated through the use of 16S rRNA gene sequencing, blood and stool samples, brain wave recordings, and MRI images of the infants’ brains.
 
The study, which is an inter-university project under the joint leadership of Angelica Berger from the Medical University of Vienna and David Berry from University of Vienna, is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children more thoroughly. The research will also continue to follow the children involved in the initial study.
 
“How the children’s motor and cognitive skills develop only becomes apparent over several years,” Berger said. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term.”