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Valentina Biagioli
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Biagioli, V.; Volpedo, G.; Riva, A.; Mainardi, P.; Striano, P. Microbiota in Newborn from Birth to Weaning. Encyclopedia. Available online: https://encyclopedia.pub/entry/54392 (accessed on 02 May 2024).
Biagioli V, Volpedo G, Riva A, Mainardi P, Striano P. Microbiota in Newborn from Birth to Weaning. Encyclopedia. Available at: https://encyclopedia.pub/entry/54392. Accessed May 02, 2024.
Biagioli, Valentina, Greta Volpedo, Antonella Riva, Paolo Mainardi, Pasquale Striano. "Microbiota in Newborn from Birth to Weaning" Encyclopedia, https://encyclopedia.pub/entry/54392 (accessed May 02, 2024).
Biagioli, V., Volpedo, G., Riva, A., Mainardi, P., & Striano, P. (2024, January 26). Microbiota in Newborn from Birth to Weaning. In Encyclopedia. https://encyclopedia.pub/entry/54392
Biagioli, Valentina, et al. "Microbiota in Newborn from Birth to Weaning." Encyclopedia. Web. 26 January, 2024.
Microbiota in Newborn from Birth to Weaning
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This entry is adapted from the peer-reviewed paper 10.3390/nu16020272

Nutrients play a crucial role in enriching and diversifying the microbiota, derived not only from solid food but also from maternal dietary patterns during gestation.

microbiota human milk oligosaccharides complementary feeding

1. Introduction

From the first moments of life, the newborn’s body begins a mutualistic relationship with numerous microorganisms. This condition represents a true “superorganism” composed of bacteria, viruses, archaea, and unicellular eukaryotes. Bacteroidetes and Firmicutes are the major bacterial phyla, with subgroups such as Fusobacteria, Cyanobacteria, Proteobacteria, Verrucomicrobia, Actinobacteria, and a few others [1]. These microorganisms colonize our entire organism, including the integumentary system and mucosal cavities (e.g., pulmonary, oral, and vaginal); however, most are found in the gastrointestinal tract (GIT). Moreover, the colon contains more than 70% of the microorganisms colonizing the GIT [2]. The intestinal microbiota represents a “vital organ”, which, owning to the numerous connective pathways such as the neural, endocrine, immunological, and metabolic pathways, can communicate with areas that are anatomically distant from one another [3].
A balanced intestinal microbial ecosystem, called eubiosis, is effective in controlling a variety of infectious diseases. Therefore, balanced nutrition from qualitative and quantitative points of view and proper food processing to preserve their organoleptic and nutritional properties are fundamental for human health and for maintaining a healthy gut microbial composition [2]. On the contrary, the prolonged use of antibiotics causes an imbalance between the different strains that make up the microbiota, referred to as dysbiosis [4], a condition characterized by a shift in the composition of commensal bacterial strains toward a more pathogenic profile [2]. This change can lead to an increase in intestinal permeability, consequently triggering an inappropriate immune response [5]. This so-called “leaky gut” is often associated with conditions such as dysbiosis and gastrointestinal symptoms, which also appear to play a key role in the pathogenesis of autism spectrum disorder (ASD) [6][7]. Moreover, scientific evidence shows that microbiome dysbiosis correlates to the pathophysiology of allergies and autoimmune disorders [8]. Notably, the contribution of the human gut microbiota in early life is fundamental for the development and maturation of the infant mucosal and immune system (Figure 1).
Nutrients 16 00272 g001
Figure 1. Developmental phases of microbiota biodiversity from delivery to weaning. Created with BioRender.com.

1.1. What Is the “Window of Opportunity”?

1.1.1. Maternal Nutrition and Infant Gut Microbiome: How Materno–fetal Exchange Influences the Development of Neonates

Pregnancy is a unique biological process that involves numerous physiological changes to support the health of both the mother and the fetus. Moreover, the placenta is a highly specialized organ, which divides the fetal and maternal environments. Historically, the placenta was considered a sterile organ, but, in recent years, new evidence has demonstrated the possible existence of a placental microbiome. In 2014, the first studies based on bacterial DNA demonstrated the existence of a placental microbiota even during full-term and normal pregnancies [9].
Metagenomics and metabolomics studies have shown that the maternal intestinal microbiota plays an important role in the transport of metabolites derived from commensal bacteria across the placental barrier and is therefore able to modulate fetal development [10]. Exogenous factors such as diet and drug intake, as well as endogenous factors such as maternal stress and alterations in the metabolic state, influence the maternal intestinal microbiota [11].
Even during a normal pregnancy, the maternal microbiota changes its composition. For example, Faecalibacterium is a producer of short-chain fatty acids (SCFAs), which tends to decrease in the last trimester of pregnancy [12]. SCFAs such as acetate, propionate, and butyrate are of fundamental importance as they provide 60–70% of the energy needs of colonocytes [13]; in particular, butyrate promotes cellular repair and regeneration processes, maintaining epithelial integrity [14][15]. 
The fetal microbiota composition is therefore strongly influenced by prenatal factors and strictly dependent on maternal lifestyle and habits. For example, smoking and a Western diet style rich in sugars, processed foods, and saturated fats negatively influence the fetal microbiota [16].
The intrauterine life and the first years of life represent a critical time to shape the newborn’s microbiota. In humans, the composition of the intestinal microbiota appears to stabilize around 2.5–4 years of life [17]. Before this stabilization occurs, the intestinal microbiota of the newborn appears to be much more susceptible to stimuli that modulate it [18][19].

1.1.2. Vaginal Delivery and Vertical Transmission of Microbiota

During natural birth, the fetus passes through the maternal vaginal canal, coming into contact with the microbial ecosystem present (vaginal and fecal). This has a long-term influence on the composition and development of the newborn’s microbiota [20].

1.1.3. Caesarean Section

During a cesarean (C-) section, the baby has increased contact with the mother’s integumentary system and with the microbes present in the hospital environment [21]. Contrary to vaginal births, C-section-delivered newborns show reduced microbiota diversity and richness, with significantly lower levels of bacterial genera such as Bifidobacterium, Lactobacillus, and Bacteroides, as well as higher levels of Staphylococcus. Interestingly, clinical studies highlight a relationship between C-section and immune disorders, such as allergies and asthma [22]. However, further studies are needed to clarify the long-term role of the altered microbiota.

2. Human Milk and Neonatal Brain Development

2.1. Macro- and Micronutrient Composition

Breast milk is made up of macro- and micronutrients specialized in supporting the physiological and metabolic functions, neural development, and the intestinal microbiota of the newborn [23]. Two weeks after giving birth, human milk is considered fully mature. Mature milk contains 6.9–7.2% carbohydrates, 3–5% fats, 0.8–0.9% proteins, and 0.2% mineral components [24] (Figure 2).
Nutrients 16 00272 g003
Figure 2. From colostrum to mature milk and their different properties.

2.2. Human Milk Oligosaccharides

Human milk oligosaccharides (HMOs) are complex, indigestible glycans present in high quantities in breast milk [25]. HMOs act as real prebiotics as they cross the intestinal lumen and are fermented by the intestinal microbiota [26]. After lactose and lipids, HMOs are the third most abundant components of human milk, with high quantities (20–25 ng/L) in HC, gradually decreasing to 5–15 ng/L in mature milk.
HMOs prevent infection with pathogenic bacteria such as Salmonella, Campylobacter, and Listeria and promote Bifidobacterium [27], thus limiting the growth of bacteria potentially harmful to the newborn [28].

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 [29] 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]. To date, scientific evidence has detected microbial metabolites in HC [30]. 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 × 105 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]. 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].

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]. 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].

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].
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].
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].

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]. 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].

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]. 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]. Brain development begins during fetal life and continues through adolescence through critical processes such as neurogenesis, synaptogenesis, and myelination [42].

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.

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Subjects: Pediatrics
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Valentina Biagioli
,
Greta Volpedo
,
Antonella Riva
,
Paolo Mainardi
,
Pasquale Striano
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Update Date: 29 Jan 2024
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