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Borrego-Ruiz et al. Microbiome Res Rep. 2025;4:20 https://dx.doi.org/10.20517/mrr.2024.78 Page 7 of 22

Figure 1. Important factors affecting microbiome abundance and richness at the early stage of life.

[66,70-73]
During the first three months of life, breastfeeding as a method of infant nutrition leads to changes in the
composition of the GM, resulting in increased levels of the genera Bifidobacterium, Corynebacterium,
Propionibacterium, Sneathia, Enterococcus, Lactobacillus, and Streptococcus, and decreased levels of
Bacteroides and Staphylococcus [59-61] . Nevertheless, formula-feed infants possess a recognizable GM
composition, mainly characterized by elevated levels of the bacterial genera Atopobium, Clostridium,
Enterococcus, Granulicatella, Lactobacillus, Bacteroides, Citrobacter, Enterobacter, Escherichia, and
Bilophila [58,59,62,63] . .

In the course of weaning, the introduction of various solid foods and novel dietary components leads to a
rise in microbial α-diversity and pH within the GM . Solid foods promote the proliferation of bacteria
[5]
capable of utilizing a broader spectrum of carbohydrates, synthesizing vitamins, and degrading
xenobiotics [57,64-66] . Consequently, the dominant members of the infant microbiome undergo a shift, although
there is a substantial difference between the GM of infants who have weaned and those who have been
breastfed for a continued period. In the initially mentioned group, the predominant genera include
Bifidobacterium, Anaerostipes, Blautia, Clostridium, Faecalibacterium, Roseburia, Ruminococcus, Bacteroides,
Bilophila, and Akkermansia. In contrast, infants who continued breastfeeding for an extended duration
exhibit higher abundances of Collinsella, Lactobacillus, Megasphaera, and Veillonella [5,57,67] . These
microbial alterations are linked to enhanced protein intake (associated with members of the family
Lachnospiraceae), heightened dietary fiber intake (connected to members of the family Prevotellacea), and
increased mucin generation (from the genus Akkermansia) . It is estimated that approximately three years
[60]
are required for the establishment of a mature and functional GM, at which point its composition resembles
that of adults [66,68,69] . Nevertheless, the structure and composition of the GM are continually and dynamically
influenced throughout life by factors such as drug use, dietary patterns, physiological changes, infectious
diseases, and lifestyle choices .

IMPACT OF EARLY-LIFE MICROBIOTA ON LONG-TERM PHYSIOLOGICAL OUTCOMES
The early establishment of microbial communities plays a crucial role in the parallel development of the
immune system and the subsequent maturation of the gut and its associated metabolic functions. Therefore,
GM dysbiosis may disrupt or alter this programming, resulting in long-term physiological responses and
health conditions . In this sense, it has been demonstrated that microbial factors influence the activity of
[11]
chemokine ligand CXCL16, which regulates the concentration of non-variable natural killer T cells in both
the colon and lungs. Furthermore, colonizing germ-free mice with a conventional microbiota during the
neonatal period protects against this accumulation . According to these authors, the early-life microbiota
[74]
initiates enduring effects, and the lack of such microbial exposure may lead to inflammatory responses later
in life that are associated with asthma and IBDs. More recently, a link has been suggested between the