**3. Gut colonization and microbiota establishment in infancy**

The first few weeks of life are very important for the gut colonization in the infant. This process will be influenced by maternal factors (weight gain during pregnancy, BMI, nutrition, microbiome composition), intrauterine state (microbiota of amniotic fluid), type of delivery (caesarean or vaginal), type of feeding later (breast milk or infant formula), and antibiotic exposure, among others (**Figure 1**).

Traditionally, the placenta had been considered a sterile organ but current studies have reported the existence of a placental microbiome [35–37]. Although the origin of the bacteria colonizing the placenta is unclear, it has been shown that the microbial community is represented by members of nonpathogenic bacteria from the phylum *Proteobacteria, Firmicutes, Bacteriodetes, Fusobacteria*, and *Tenericutes* [38].

Recently, placenta microbiota has been associated with preeclampsia development during pregnancy and with preterm birth, which highlights the importance of the close relationship between the microbiota and pregnancy [39]. A placental dysbiosis during pregnancy as a consequence of excess weight gain could have a major influence on the colonization and establishment of gut microbiota community on the infant [40].

Because these findings are very recent, the effects of the bacterial profile modification by probiotic supplementation during pregnancy and the effects on placental microbiome modulation are still unknown and further studies are needed.

After birth, it is known that meconium is not sterile and harbors a particular microbial community, characterized by a higher abundance of *Firmicutes* compared to *Proteobacteria* in early fecal samples [41].

A study showed that the mode of delivery (caesarean or vaginal) did not affect the diversity of the microbiota from meconium, in contrast, these samples presented a lower species diversity

Infant gut microbiota will not be only influenced by mother's BMI, but also by the mode of delivery [32]. A study indicated that excess maternal prepregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, enriched in genus *Bacteroides* and depleted in genus *Enterococcus, Acinetobacter, Pseudomonas*, and

Subsequent to delivery, it has been shown that the type of feeding is one of the major factors

The establishment of the microbial community allows the maturation of the immune system as it has been demonstrated in germ-free (GF) animal models, where commensal microorganisms are required for the development of a fully functional immune system, which affects

In conclusion, the mother environment influences the offspring phenotype of her offspring, independently of his genotype. So, not only genetics will influence offspring gut microbiota

The first few weeks of life are very important for the gut colonization in the infant. This process will be influenced by maternal factors (weight gain during pregnancy, BMI, nutrition, microbiome composition), intrauterine state (microbiota of amniotic fluid), type of delivery (caesarean or vaginal), type of feeding later (breast milk or infant formula), and antibiotic

Traditionally, the placenta had been considered a sterile organ but current studies have reported the existence of a placental microbiome [35–37]. Although the origin of the bacteria colonizing the placenta is unclear, it has been shown that the microbial community is represented by members of nonpathogenic bacteria from the phylum *Proteobacteria, Firmicutes,* 

Recently, placenta microbiota has been associated with preeclampsia development during pregnancy and with preterm birth, which highlights the importance of the close relationship between the microbiota and pregnancy [39]. A placental dysbiosis during pregnancy as a consequence of excess weight gain could have a major influence on the colonization and

Because these findings are very recent, the effects of the bacterial profile modification by probiotic supplementation during pregnancy and the effects on placental microbiome modula-

After birth, it is known that meconium is not sterile and harbors a particular microbial community, characterized by a higher abundance of *Firmicutes* compared to *Proteobacteria* in early

A study showed that the mode of delivery (caesarean or vaginal) did not affect the diversity of the microbiota from meconium, in contrast, these samples presented a lower species diversity

modulating infants gut microbiota and it will be discussed in Section 4.

development, but also mother's lifestyle before, during, and after pregnancy.

**3. Gut colonization and microbiota establishment in infancy**

many physiological processes within the host [34].

exposure, among others (**Figure 1**).

fecal samples [41].

*Bacteriodetes, Fusobacteria*, and *Tenericutes* [38].

establishment of gut microbiota community on the infant [40].

tion are still unknown and further studies are needed.

*Hydrogenophilus* [33].

268 Adiposity - Omics and Molecular Understanding

**Figure 1.** Maternal and environmental elements affecting the onset and modulation of the gut microbiota in the newborn infant. A plethora of factors during pregnancy can negatively influence the neonate's gut microbiota composition and function. Furthermore, environmental factors, such as mode of delivery and feeding modality can significantly drive the neonate's gut microbiota.

and a higher variation among samples in comparison with adult feces [42]. These results indicate that the microbial contact during perinatal life may imprint the offspring microbiota and immune system in preparation for the much larger inoculum transferred during vaginal delivery and breast-feeding.

As mentioned in the previous section, the mode of delivery is going to favor the establishment of a specific microbiota. Previous studies have demonstrated that gut microbiota of infant born through vaginal delivery is similar to maternal gut and vaginal microbiota; conversely, the infants born by caesarean section have a gut community more similar to bacteria from maternal skin or the hospital environment [43].

Regarding the mode of delivery, epidemiological studies suggest that caesarean delivery is associated with increased risk of overweight and obesity later in life [44]. A study has found that caesarean section delivery was associated with adiposity at 6 weeks of age, being this association stronger in children born from obese mothers and having higher risk of obesity and overweight at 11 years old [45]. Although the mode of delivery may affect the colonization of the intestinal microbiota in the baby and will increase the risk for later obesity development, it has been found that perinatal exposition of the infant born by caesarean section respect to the vaginal discharge, can partially restore its gut microbiota and resembles to babies born by vaginal delivery avoiding the problems that this entails [46].

The microbiota of the babies by the end of the first year of life presents a different microbial profile in comparison to adults. The initial gut composition of the infant is simple, dynamic, and very unstable and undergoes marked fluctuations influenced by external factors [47]. At the beginning, the gut environment is aerobic, but through colonization, the oxygen level is reduced generating a suitable environment for the growth of anaerobes [48]. The intestinal microbiota of neonates is characterized by low diversity and a relative dominance of facultative anaerobes of the phyla *Proteobacteria* and *Actinobacteria* [49]. After birth, the phyla *Firmicutes* and *Bacteroidetes* increase their diversity and dominance, reaching over 3 years old a total resemblance to the adult in terms of composition and diversity [50]. These results indicate that dietary intake during the first 1500 days of life is a critical factor in the establishment of gut microbiota community and its role in the development of obesity is a matter of research and discussion.
