Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.
Complex interplay: the gut-immune-brain axis
The gut, the brain, and the immune system all develop at the same time in the early stages of life. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We looked into the role of this axis in the brain development of extreme preterm infants,” says David Seki, the study’s first author. “In healthy people, the microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses, and other microbes — are in equilibrium; however, shifts are quite likely to occur, especially in premature babies whose immune system and microbiome have not been able to fully develop,” explains t.
Patterns in the microbiome provide clues to brain damage
“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,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often appear before changes in the brain, suggesting a critical time window during which brain damage in extremely premature infants can be avoided or at least delayed.”
Comprehensive study of the development of extremely premature infants
The biomarkers that the interdisciplinary team was able to identify provide starting points for the development of appropriate therapies. “Our findings suggest that excessive Klebsiella growth and associated elevated??-T-cell levels can exacerbate brain damage,” says Lukas Wisgrill, a neonatologist at the Medical University of Vienna’s Division of Neonatology, Pediatric Intensive Care Medicine, and Neuropediatrics. “We were 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,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.
Research continues with two studies
The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (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 even more thoroughly. Furthermore, the researchers will continue to follow the children who participated in the first study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”