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Page 10 of 22 Borrego-Ruiz et al. Microbiome Res Rep. 2025;4:20 https://dx.doi.org/10.20517/mrr.2024.78

pathobionts that reduce nutrient absorption, potentially causing epithelial damage and promoting
[121]
inflammation, which in turn compromises intestinal barrier permeability . This situation can escalate
systemic inflammation, a key factor in the development of ACVDs [129,130] .

ACVDs are characterized by chronic inflammation in which lipids are retained within the arterial wall,
leading vascular smooth muscle cells to form a collagenous, fibrous cap that becomes infiltrated by immune
[131]
cells, such as mast cells, T cells, and macrophages . This atherosclerotic process, a primary contributor to
ACVDs, begins early in life and is linked to a broad range of risk factors, such as diabetes, hypertension,
persistent low-grade inflammation, and GM imbalances . Therefore, the impacts of gut metabolites and
[132]
gut dysbiosis underscore the influence of the GM on ACVDs by promoting inflammation and altering
cholesterol metabolism. Bacterial presence has been detected within atherosclerotic plaques , contributing
[133]
to the origination of atherogenesis by stimulating platelet aggregation and thrombus formation, or by acting
via their structural components like LPS, to activate an inflammatory cascade by heightening the expression
patients include Bifidobacteriaceae, Enterobacteriaceae, and Lachnospiraceae
[134]
of IL-1β . Diverse studies have examined the indirect impact of the GM on ACVD development via its
metabolites [short-chain fatty acids (SCFAs), trimethylamine, trimethylamine-N-oxide (TMAO), and bile
acids (BAs)], which regulate host systemic inflammation, activate the innate immune system, and shape the
adaptive immune response [121,135,136] . These microbial metabolites can function as signaling molecules,
binding to specialized receptors on remote organs or influencing endocrine pathways through indirect
interactions with other endocrine molecules .
[134]
IMPACT OF ELS ON THE GM
ELS encompasses a range of adverse experiences occurring before the age of 18, including forms of abuse
(psychological, physical, or sexual), neglect (both emotional and physical), persistent family dysfunction,
[138]
and socioeconomic struggles . In addition, ELS is a predictor of adult depression , and it is related to the
[137]
magnitude of depressive symptoms and the duration of the depressive trajectory . Several studies have
[139]
[140]
shown that ELS provokes GM dysbiosis , and that the GM exerts a pivotal role in the development of
depression through the gut-brain axis communication [141,142] . The interplay between GM and depression
constitutes a reciprocal process; depressed patients exhibit altered GM composition , and the
[143]
transplantation of GM from individuals with depression can result in anxiety and depressive behaviors in
[144]
receptor rodents .
The human GM composition shows marked differences between individuals with depression and healthy
controls, but there are controversial results across studies [145,146] . At the phylum level, findings from most
studies indicate that individuals with depression exhibit a significantly higher relative abundance of
Actinomycetota compared to controls [147-152] . At the family level, the most abundant taxa in depressed
[147-149,152,153] . At the genus level,
the most abundant bacteria are Alistipes, Bacteroides, Bifidobacterium, Blautia, Clostridium, Eggerthella,
Holdemania, Oscillibacter, Parabacteroides, and Streptococcus [143,148-156] . On the other hand, members of the
phylum Bacteroidota and genus Faecalibacterium seem to be inversely related to depression [147,148,150-153] . More
recently, Kraaij et al. performed a cross-sectional study involving 1,784 ten-year-old children from the
Netherlands to define the relationships between the GM and mental health issues in children . Although
[157]
lower gut microbial diversity and richness were associated with internalizing problems and anxious/
depressed behavior issues, these associations were not significant. These authors did not find definitive
evidence linking GM diversity, taxonomic features or functions, and mental health conditions in the
pediatric cohort. However, they noted suggestive findings indicating a reduction in the genera that have
previously been related to psychiatric disorders, including Anaerotruncus, Hungatella, and Oscillospiraceae.
No associations were found between ELS and the GM, although socioeconomic stress was the only ELS