The early development of the gut, the brain and the immune system are closely interrelated. 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 investigated the role this axis plays in the brain development of extreme preterm infants," says the first author of the study. "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 in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain," explains the microbiologist and immunologist.
"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 the author. "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 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.
The authors found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants.
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 bacterium Klebsiella and the associated elevated γδ-T-cell levels can apparently exacerbate brain damage," explains the senior author. "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," the author adds.
"How the children's motoric and cognitive skills develop only becomes apparent over several years," explains another author. "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 the lead author. "Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that."
Gut bacteria influence brain development
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