[52], thus limiting the growth of bacteria potentially harmful to the newborn [48].
2.3. Other Bioactive Compounds
Some bioactive components of breast milk such as insulin-like growth factors (IGFs) 1 and 2 act as energy substrates for newborns, promoting the growth and development of various tissues. Among the bioactive components, there is lactoferrin, a glycoprotein that binds iron and has antimicrobial activity.
Furthermore, secretory (S)IgA and SIgG are the most abundant immunoglobulins in milk, providing support to the newborn’s immune functions [53] by preventing the adhesion of pathogens to the surface of epithelial cells. SIgA is present at concentrations up to 12 mg/L in HC.
2.4. Breast Milk Microbiome
Initially, human breast milk (HBM) was considered a sterile fluid, and the presence of bacteria was considered to be contamination or infection
[24][44]. To date, scientific evidence has detected microbial metabolites in HC
[30][56]. This discovery has led to growing interest in the HMB microbiome.
After the vaginal birth canal, the HBM is the second source of microbes for the newborn. Breastfed babies have been predicted to consume up to 8 × 10
5 bacteria each day. There are various mechanisms proposed to explain the transmission of the microbiota through breastfeeding, including contamination from the mother’s integumentary system and retrograde flow from the newborn oral cavity to the ductal tissue
[24][44]. In support of these hypotheses, notable similarities have been found between the adult skin microbiome and the milk microbiome, in particular the presence of
Corynebacterium and
Staphylococcus.
3. Infant Formula
3.1. Macronutrients in Infant Formula
Even though breastfeeding is the first choice for the health of the newborn, many factors can influence the decision, such as medical, occupational, or family support problems and complications. When breastfeeding is not an option, infant formula (IF) becomes part of the newborn’s nutrition.
Most of the constituent proteins in IF derive from bovine milk, which has fewer essential amino acids than HBM. The protein content of IFs of bovine origin varies between 2 and 3 g/100 mL, higher than the protein level present in HBM (1.4–1.6 g/100 mL in HC and 0.8–1.0 g/mL in mature milk). This excess of proteins and amino acids overstimulates the β-pancreatic cells and is strongly associated with early adiposity and a greater risk of becoming overweight in adulthood
[31][57].
3.2. Supplements in Infant Formula: Probiotics, Prebiotics, and Postbiotics
In recent years, research has increasingly focused on the effect of prebiotics and probiotics on the infant microbiota. These studies, combined with a growing interest from industries in IF, have led to the continuous improvement in IF to create a formulation that resembles HBM as much as possible. New IFs have currently been developed with enrichment in bioactive ingredients such as probiotics, prebiotics, and postbiotics.
In October 2013, the International Scientific Association for Probiotics and Prebiotics (ISAPP) re-examined the concept of probiotics, redefining them as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. This definition is inclusive of a wide range of microbes and therapeutic applications. The seven most commonly used genera in commercial products are
Bifidobacterium,
Saccharomyces,
Streptococcus,
Escherichia,
Lactobacillus,
Enterococcus, and
Bacillus [32][59]. Prebiotics, on the other hand, are food substrates that, once ingested, are selectively fermented by certain microbial strains, conferring benefits to the host. The most commonly used prebiotics include galactooligosaccharides (GOS), fructooligosaccharides (FOS), and inulin.
3.3. Infant Formula, Risks, and Future Directions
The use of IF stimulates glucose metabolism, increases insulin sensitivity, and causes early advanced adiposity that persists into adulthood. However, further studies are needed to delve into the safe dosages and beneficial effects in pediatric disorders and premature infants to create more standardized protocols for this age group
[33][66].
4. Dietary Nutrients Shape the Gut Microbiota: From Infancy to Childhood
4.1. Microbiota Maturation during Weaning
Malnourished and under- or over-nourished infants and children develop an immature intestinal microbiota, which can compromise child growth
[34][67].
The transition to solid foods implies an increase in the intake of proteins, carbohydrates, lipids, and fibers, which leads to an increase in microbial richness and diversity. For example, a randomized control trial demonstrated that the introduction of solid foods (including meat, cereals, and fruit) led to an increase in the diversity of the gut microbiota
[35][68].
During this transition, the count of milk-related bacteria, such as
Bifidobacterium,
Lactobacillaceae, and
Enterobacteriaceae, decreases, while bacteria such as
Bacteroides,
Akkermansia, and
Ruminococcaceae, which are capable of fermenting and digesting the more complex nutrients, are introduced during weaning and expand
[36][69].
4.2. Establishment of Nutritional Habits from Solid Food Introduction
It is known that the mother’s eating habits and qualitative choice of nutrients during pregnancy are essential for the development of the newborn’s taste and olfactory preferences
[37][72]. The olfactory system, which includes the olfactory bulbs of the brain that are already functioning at the 24th week of gestation, develops in parallel with that of taste: swallowing and breathing the amniotic fluid offers the fetus the flavors and odors of the food consumed by the mother
[38][73].
4.3. Nutrient–Microbiota Interactions and Brain Development during Early Life
Microbial signals are crucial not only for intestinal eubiosis but also for the healthy and correct development of neuronal circuits in the brain
[39][78]. Intestinal microbes communicate with the central nervous system (CNS), secreting signaling molecules that move through the circulatory system and crossing the intestinal epithelium and the blood–brain barrier (BBB)
[40][41][79,80]. Brain development begins during fetal life and continues through adolescence through critical processes such as neurogenesis, synaptogenesis, and myelination
[42][81].
5. Conclusions
Starting from intrauterine life, the gut microbiota composition and biodiversity are influenced by environmental factors and nutrition. Beyond the different dietary regimes, the vastness and biodiversity of the microbial world that accompanies us throughout our lives cannot be addressed with a “one-size-fits-all” approach. The period of gestation and the birth of the newborn represents a window of opportunity to modulate the health status of the newborn through noninvasive and inexpensive methods such as education on healthy nutrition for microbial biodiversity.