*4.3. Preterm*

Preterm babies that, thus, have gone through stressful situations similarly show lower levels of *Lactobacillus* spp. [144], and simultaneously have a significant increase in the prevalence of ADHD [58,145,146]. More specifically, Barrett et al. showed an increased abundance of *Proteobacteria* spp., while discovering undetectable levels of *Lactobacillus* spp. and *Bifidobacteria* spp. [144,147]. Chou et al. discovered that certain strains of *Lactobacillus* spp. show a protective trait towards the CNS. Preterm babies received strains of *Lactobacillus reuteri* and *Lactobacillus rhamnous* as probiotics for six weeks. This treatment resulted in a significantly reduced number of babies with neurological aberrations

at one year of age in comparison to the group fed with *Lactobacillus acidophilus* and *Bifidobacterium infantis* [148].

It is widely known that preterm infants own an immature immune system as the innate and adaptive immune system has not developed fully. Due to their immature immune response and their usual extended hospital stay, infants are highly susceptible to nosocomial spread infections [149]. The increased number of infections may impair the neurodevelopment, and thus, might influence the development of the most common neurodevelopmental disorder ADHD. In addition to this, the weeks before term delivery (between 37 0/7 and 41 6/7) [150] represent an important stage in the neurodevelopment of the brain usually occurring in the protective womb of the mother [151,152]. Thus, preterm babies suffer from underdeveloped brain structures that in combination with postnatal complications, such as infections can lead to cell death of neurons, and finally lead to a decrease in the volume of specific areas of the brain [153].

As the prevalence of infection in premature newborns is high, the use of therapeutic antibiotics is similarly increased. Antibiotics have been associated with altering functions in the host s brain [154], while simultaneously, they are notoriously known for reducing the diversity of the microbiota [155]. Nevertheless, the direct effects of a lower microbiota diversity on the neurodevelopment have still not been thoroughly researched on, and thus, a concrete correlation cannot be made.

To summarize, a preterm baby is exposed to increased levels of stress, may have underdeveloped brain structures and owns an immature immune system. All of these result in a higher susceptibility to infections, and finally may lead to increased exposure to therapeutic antibiotics. These factors influence the neurodevelopment either directly through inflammatory processes during infections or indirectly by changing the composition of the gut microbiome.
