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Borrego-Ruiz et al. Microbiome Res Rep. 2025;4:20 https://dx.doi.org/10.20517/mrr.2024.78 Page 9 of 22

[104]
In addition, epigenetic shifts linked to microbiota in the early stages of development , and also the
[105]
influence of the GM on brain development, must be considered in the programming of obesity .
According to some preclinical and clinical studies, the most important factor influencing metabolic diseases
[106]
is antibiotic therapy in early life , which significantly alters the GM [100,107,108] . However, one study involving
a substantial cohort of over 260,000 subjects reported that childhood obesity was positively associated only
[109]
with non-treated infections rather than with antibiotic intake during infancy . To resolve these conflicting
findings, further evidence from human epidemiologic studies is necessary to conclusively determine the
causal relationship between antibiotic-driven dysbiosis during early life and subsequent metabolic effects in
later life.

T1D
Dysbiosis of the GM in early infancy has also been linked to various chronic diseases that may emerge later
in life. T1D is an autoimmune disease that results from an autoimmune response in which autoreactive T
[122,123]
cells partially or completely destroy the beta cells responsible for insulin production within the islets of the
pancreas, and it is triggered by genetic and environmental factors [110,111] . Accumulating evidence from both
preclinical and human studies suggests a role for GM in the onset of this condition [112,113] . Microbial studies
in T1D have shown a lower microbial diversity and a significant difference in the Bacillota/Bacteriodota
phyla ratio, and also diminished levels of the butyrate producer Faecalibacterium prausnitzii in children
with diabetes [114,115] . Interestingly, several studies have suggested that early-life gut colonization may
[116]
influence the course of T1D development and is also involved in the pathophysiology of this disease . In
the DIABIMMUNE study, children from different geographical contexts, specifically Estonia, Finland, and
Russia, who had an HLA predisposition to autoimmune diseases, were examined [117,118] . The children who
developed T1D showed a reduction in α-diversity and elevated levels of Blautia, Rikenellaceae,
Ruminococcus, and Streptococcus, while Coprococcus eutactus and Dialister invisus were absent. A separate
study involving 33 infants at risk for T1D revealed a reduction in bacterial diversity and an increase in pro-
inflammatory bacterial species, including Ruminococcus gnavus and Streptococcus infantarius . In
[119]
addition, the researchers observed heightened levels of human β-defensin 2, an antimicrobial molecule
synthesized during inflammation, in those children who went on to develop T1D.

IBDs
IBDs are hyperimmune, multifactorial diseases that include Crohn’s disease and ulcerative colitis. Both
disorders are related to inflammation and changes in the GM (e.g., decreased microbial diversity and lower
abundance of Roseburia) and have a strong genetic basis . These diseases may first appear in childhood
[120]
[121]
and adolescence and have a lifelong chronic, relapsing course . Several factors have been reported to be
associated with the development of IBDs in childhood, such as exposure to antibiotics and cigarette smoke
during fetal life, and also breastfeeding . Although infants born to mothers with IBDs showed an
increased abundance of members of the phylum Pseudomonadota and a decreased abundance of
bifidobacteria during the first 3 months of life , it is still not clear whether these associations are causal or
[124]
interrelated, as the persistent inflammation of IBDs may affect the GM rather than the dysbiosis that causes
IBDs .
[125]

ACVDs
Specific conditions in infancy, including preterm birth, malnutrition, or the colonization of the GM, may
increase the risk for an individual to develop ACVDs later in life . Malnutrition and changes in the GM
[126]
composition are closely related, as a decline in commensal gut bacteria, such as Bifidobacterium, can result
in poor digestion, and in turn, decreased use of dietary carbohydrates and diminished vitamin synthesis
may contribute to malnutrition [126,127] . In addition, elevated levels of Pseudomonadota in preterm infants
have been identified in certain adults with ACVDs . Phylum Pseudomonadota contains several
[128]