*4.4. Breastfeeding vs. Formula Feeding*

Studies have associated breastfeeding with a lower prevalence of ADHD [156]. In contrast, formula-fed newborns showed a strong correlation with ADHD diagnosis [157–159]. The nutritious breast milk not only contains human milk oligosaccharides acting as prebiotics important for establishing a healthy gut microbiome, but also consists of vitamins and antibodies [160]. The latter being important in the first couple of months for the maturation of the innate immune system of the newborn [161]. Additionally, breast milk is marked to have a rich fat content due to its high levels of long-chain fatty acids, which are said to have protective effects on the CNS and the development of ADHD [162,163]. The gut microbiota of breastfed infants is less diverse in comparison to formula-fed infants [164]. Importantly, various groups utilizing differing methods for microbiome analysis, such as 16S sequencing or cytogenic FISH technique discovered that in both groups, the most prevalent genus is *Bifidobacterium* [122,164,165].

A systematic review by Guaraldi et al. showed that bottle-fed infants have a higher number of *Escherichia coli*, *Clostridium di*ffi*cile*, *Bacteroides* spp. and *Lactobacilli* [166]. As seen in Table 3, research papers demonstrated that increased levels of *Lactobacillus acidophilus* [122], *Streptococcus*, *Veillonella parvula* [164], and*Clostridium coccoides*[165], were found in formula-fed infants. Although *Bifidobacterium* is the most prevalent genus found in both groups, breastfed infants show more than double of *Bifidobacteria* cells in comparison to formula-fed infants [164]. *Bifidobacterium infantis* has protective properties against pathogens as it supports the barrier function of the mucosa and concurrently has anti-inflammatory properties, thus, promotes a healthy immunological response [167,168].

Although the effect on the microbial composition could be the main cause of developing ADHD when being formula-fed, one has to consider the fact that other ingredients in the formula may also act as important influences. One study found that there were more cases of ADHD in formula-fed infants in 2007, than in December 2011. During the latter, the neurotoxic chemical Bisphenol A (BPA) was significantly reduced in formula cans and baby bottles in comparison to the former, suggesting that BPA might be the actual trigger of the correlation [169].


**Table 3.** Listing the different genera, predominantly found in formula-fed vs. breastfed infants. The arrow ↑ describes that this genus is increased in variously fed infants, while '-' represents that there is no significant change in this genus. One can clearly see that microbial diversity is increased in formula-fed in comparison to breastfed infants. *p* levels less than 0.05 were considered statistically different.

In summary, studies show that breastfeeding correlates negatively with the risk of developing ADHD, whereas formula-feeding increases this risk. Nevertheless, despite the highly nutritious content of breast milk, the gut microbiota of breastfed infants seems less diverse, but still contains the same or higher amount of protective components than formula-fed infants. Thus, alteration of the microbiome composition could potentially be a reason for the positive correlation between formula-feeding and the risk of developing ADHD.
