Gut microbiome patterns provide clues to brain damage in extremely preterm infants

Extremely premature infants are at high risk of brain damage. Researchers at the University of Vienna and the University of Medicine in Vienna 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 overgrowth of the gastrointestinal tract with Klebsiella bacteria is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies. The study is now published in the journal Cell Host & Microbe.

Complex interaction: the gut-immunity-brain axis

The early development of the gut, brain and immune system are closely linked. Researchers call this the gut-immunity-brain axis. Gut bacteria cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses. In addition, the intestine comes into contact with the brain via the vagus nerve as well as via the immune system.

We have studied the role that this axis plays in the brain development of very premature babies. Microorganisms in the gut microbiome – which is a vital collection of hundreds of species of bacteria, fungi, viruses, and other microbes – are in balance in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to fully develop, changes are very likely to occur. These changes can have negative effects on the brain “,

David Seki, first author of the study, microbiologist and immunologist

Microbiome models 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 damage,” adds David Berry, microbiologist and research group leader at the Center for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as operational director of the Joint Microbiome Facility at the Medical University of Vienna and the University of Vienna. “Crucially, such patterns often appear before changes in the brain. This suggests a critical window of time during which brain damage in extremely premature infants can be prevented from getting worse or even prevented. “

In-depth study of the development of extremely preterm infants

The starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the Klebsiella bacteria and the associated high levels of γδ-T cells can apparently exacerbate brain damage,” says Lukas Wisgrill, neonatologist in the division of Neonatology, Pediatric Intensive Medicine and Pediatric Neuropediatrics of the pediatric department. and Adolescent Medicine at the Medical University of Vienna. “We were able to trace these patterns because, for a very specific group of newborns, for the first time, we explored in detail how the gut microbiome, immune system, and brain develop and how they interact in this process.” , he adds. . The study followed a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using cutting-edge methods – the team examined the microbiome using 16S rRNA gene sequencing, among other methods – the researchers analyzed blood and stool samples, brain wave recordings (eg aEEG) and MRI images of infant brains.

Research continues with two studies

The study, which is an interuniversity cluster project under the joint leadership of Angelika Berger (University of Medicine Vienna) and David Berry (University of Vienna), is the starting point of a research project that will investigate the microbiome and its importance for the neurological development of prematurely born infants in even more depth. In addition, researchers will continue to follow the children in the original study. “The development of motor and cognitive abilities in children does not appear until after 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 study with great interest and open-mindedness, ”says David Seki.“ In the end, that’s the only reason we were able to get this important information. We are very grateful for that. “