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Page 6 of 22 Borrego-Ruiz et al. Microbiome Res Rep. 2025;4:20 https://dx.doi.org/10.20517/mrr.2024.78

probiotic mixture administered to 1,099 preterm infants led to a higher prevalence of probiotic species
[40]
during supplementation, but these differences were not sustained after cessation . Perinatal probiotic
treatment in children at high risk for atopic disease had minimal effects on GM composition during the
supplementation period. No lasting differences were identified by the authors, suggesting that, regardless of
intervention or atopic disease status, children follow a common microbiota development trajectory over
time, influenced by age, which persists between two and six years of age. Avershina et al. administered
L. rhamnosus strain GG in 48 mother-infant pairs, finding a greater relative abundance of this bacterium at
[41]
10 days and 3 months, but no significant differences in microbiota diversity at 12 months or 2 years . The
authors concluded that the late-colonizing OTUs were acquired at a later stage and not at birth. Korpela
et al. tested a probiotic mixture and prebiotic in 96 mother-infant pairs, showing that in breastfed infants,
[42]
probiotics increased Lactobacillus and Bifidobacterium relative abundance . In this regard, in formula-fed
infants, Bifidobacterium abundance was lower, with other taxa showing increases. The findings of the study
demonstrate the efficacy of probiotic supplementation in conjunction with breastfeeding in rectifying
characteristics of the gut microbiota central to infection risk.
adverse disruptions in the composition and function of the infant’s microbiota. These changes may result
from antibiotic treatments or cesarean delivery. In turn, Pärnänen et al. found no significant impact of two
probiotic combinations on antibiotic resistance genes . The authors posited that infants inherit their
[43]
mothers’ legacy of past antibiotic consumption, a phenomenon transmitted genetically. However, the
composition of the microbiota remains a significant factor in determining the overall resistance load.
Plummer et al. studied 1,099 preterm infants, showing higher Bifidobacterium and reduced Enterococcus in
[44]
the probiotic group during supplementation . The authors identified a correlation between increased
Bifidobacterium abundance in the immediate postnatal period and a reduced risk of necrotizing
enterocolitis in very preterm infants. Furthermore, Castanet et al. investigated the effects of different
nutrient combinations in infants fed starter formula, finding that prebiotic components had a greater
[45]
impact on microbiota shifts than probiotics . A correlation was noted between alterations in microbiota
composition and the gut maturation marker calprotectin. Supplementation with the prebiotic seems to
promote a more advanced state of gut maturation, resembling that observed in breastfed infants. Moreover,
Martí et al. conducted a study in which they administered a L. reuteri supplementation to 132 extremely
preterm infants, noting increased bacterial diversity but no significant long-term effects . Overall,
[46]
probiotics appeared to have the potential to confer benefits by modulating the composition of the GM
during the initial postnatal period (the first month) in infants with extremely low birth weight. Lastly,
Bargheet et al. tested probiotic effects in preterm infants, showing improved microbiota and resistome
similarity to term infants, but both probiotics and antibiotics increased the presence of mobile genetic
[47]
elements . The authors concluded that prolonged hospitalizations, antibiotic use, and probiotic
interventions contribute to dynamic alterations in both the resistome and mobilome, which are key

The establishment of the GM infant shape is impacted by a variety of external, maternal-related, nutritional,
and pharmacological agents [48-50] . Following birth, the initial microorganisms that colonize the body of the
infant are derived from the maternal microbiota, including sources such as the vagina, skin, mouth, and
feces, along with microbes from the immediate environment . The predominant bacterial composition of
[51]
the GM of vaginally delivered newborns is the genera Bifidobacterium, Collinsella, Clostridium,
Lactobacillus, Streptococcus, Veillonella, Bacteroides, Parabacteroides, Prevotella, Sneathia, Escherichia,
Shigella, and Akkermansia [51-54] . Alternatively, the GM of cesarean-born infants is primarily composed of
Corynebacterium, Propionibacterium, Slackia, Staphylococcus, Streptococcus, Veillonella, Enterobacter, and
Haemophilus [5,21,55-58] . Figure 1 presents several important factors affecting microbiome abundance and
richness at the early stage of life.