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Borrego-Ruiz et al. Microbiome Res Rep. 2025;4:20  https://dx.doi.org/10.20517/mrr.2024.78  Page 13 of 22

               adversities has been linked to altered GM profiles in children, with specific microbial taxa associated with
               adversity exposure. These alterations are reflected in the child’s socioemotional functioning, supporting the
               idea that intergenerational transmission of adversity may affect mental health through changes in GM
                      [177]
               function . Moreover, variations in the GM, along with inflammatory markers, may represent mechanistic
               pathways for the observed health outcomes. For instance, GM characteristics could predict social
               disadvantage and psychosocial stress, highlighting microbial imbalances as mediators of early adversity
               effects . This evidence suggests that ELS can induce microbial changes predisposing individuals to
                    [178]
               conditions like asthma and diabetes.

               ELS has also been linked to later-life health issues, including inflammatory diseases and cardio-metabolic
               disorders [121,181] . In addition, ELS-induced GM dysbiosis plays a particularly crucial role in depression
               through gut-brain axis communication [142,183] . Inadequate or insufficient microbial exposure in early life can
               lead to inflammatory responses associated with several conditions, such as allergies, obesity, T1D, and
               generalizability and comparability of results. Further research employing consistent stressors, validated
               cardiovascular diseases [121,184-186] . Furthermore, childhood trauma has been shown to negatively impact stress
               recovery, with heart rate indices indicating impaired recovery, further emphasizing the long-term effects of
               ELS on health. These findings point to enduring impacts on both physical and psychological well-being in
               adulthood . Thus, understanding the mechanisms behind early-life GM dysbiosis is essential for
                        [179]
               identifying potential interventions to mitigate the risk of chronic diseases.

               Maternal stress is another key factor influencing both maternal and infant microbiota. Prenatal and
               postnatal stress can lead to volatile shifts in infant GM that are specific to certain developmental stages ,
                                                                                                      [180]
               indicating a complex relationship between stress and microbiome development, as well as potentially
               exacerbating the risk of chronic diseases in offspring. Early exposure to maternal stress may predispose
               individuals to conditions like obesity, cardiovascular diseases, and neurodevelopmental disorders, with a
               disrupted GM playing a central role . Furthermore, stress-related changes in the microbiome may involve
                                             [181]
                                                                   [182]
               epigenetic modifications that adapt the gut-brain axis to stress .
               Although several studies have reported a connection between ELS and the GM during prenatal and
               postnatal periods, a unified microbiome signature linked to either prenatal or postnatal stress has not yet
               been completely established [177,178,180] . This variability in findings is likely attributable to a range of
               methodological differences, including variations in experimental designs, age groups, geographical
               locations, ethnic backgrounds, assessment tools, timing of sample collection, analysis techniques, sample
               sizes, and the nature of stressors examined. In addition, differences in microbial composition across regions
               or populations, as well as the source of the samples (e.g., human vs. animal models, or hospital vs.
               community-based samples), can contribute to observed inconsistencies. These factors may impact the

               stress metrics, and high-resolution microbiome analyses is essential to establish clear connections between
               stress and the human GM [187,188] .

               Mulder et al. found that specific domains of ELS, such as socioeconomic stress, presented limited evidence
               of association with the GM, suggesting that other factors may also be implicated . However, the limited
                                                                                    [158]
               number of longitudinal studies and controlled intervention trials on this topic makes it difficult to establish
               a clear causal relationship. Consequently, future research is necessary to establish causality and determine
               whether various modifiable factors might be effectively targeted to improve gut health, particularly in
               children facing heightened contextual stress or adverse conditions. Understanding the mechanisms by
               which these factors influence the GM is crucial, as it could facilitate the development of customized
               interventions that mitigate the adverse effects of ELS.
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