Emerging evidence indicates that the microbial colonization of the human body during early life plays a crucial role in the maturation of metabolic, immune, and developmental pathways (Belkaid and Hand, 2014). Changes in gut microbiota composition have been associated with short- and long-term health conditions, including obesity, asthma, metabolic syndrome, chronic inflammatory diseases, and neurodevelopmental disorders (Stinson, 2020). Therefore, early life is recognized as a "window of opportunity" for modulating gut microbiota to improve health, and identifying external factors that can influence the establishment of early-life gut microbiota is of utmost importance.
Traditionally, the fetal gut has been thought to be sterile at birth; however, recent studies have identified microorganisms in meconium (Hu et al., 2019; Turunen et al., 2024). These microbes may originate during the fetal stage from the maternal environment, such as the amniotic fluid or placenta, rather than being acquired solely after birth. This challenges the long-held belief of a "sterile womb" (Perez-Munoz et al., 2017). Exposure to a poor intrauterine environment has been linked to alterations in the gut microbiota of infants (Wang et al., 2020), and maternal stress contributes to these unfavorable conditions (Wang et al., 2020). Additionally, evidence from animal studies supports the hypothesis that maternal stress can alter the microbiota of offspring. For example, rhesus monkeys exposed to maternal vocal intimidation during pregnancy had lower relative abundances of Bifidobacteria and Lactobacillus (Bailey et al., 2004). However, research at the human level is still in its infancy (Beijers et al., 2014).
A few researchers have shown evidence of an association between maternal stress and offspring gut microbiota (Aatsinki et al., 2020; Hu et al., 2019; Zijlmans et al., 2015). The first exploration of this association found that infants born to mothers who experienced high prenatal cumulative stress had higher relative abundances of Proteobacteria and lower relative abundances of Bacteria and Bifidobacteria (Zijlmans et al., 2015). However, research has mainly focused on intrapersonal stress, such as maternal anxiety and depression (Aatsinki et al., 2020; Hu et al., 2019); hence, the role of interpersonal stress, including negative life events during pregnancy and adversities during childhood, has not been adequately investigated (Bush et al., 2023).
Stress is a multidimensional concept, especially from a life course perspective (Monk et al., 2019), and the specific source or type of stress across studies might explain the variations between their findings. Childhood and pregnancy are sensitive periods for women, during which exposure to stressors may affect their bodies and behavior, potentially affecting offspring development and health (Bush et al., 2023). Several studies have reported that the children of mothers with a history of childhood adversity exposure exhibit a higher prevalence of adverse birth outcomes, neurodevelopmental and behavioral problems, and poorer general health (Bouvette-Turcot et al., 2015; Flory et al., 2011; Myhre et al., 2014; Smith et al., 2016). Therefore, adverse childhood experiences should not be overlooked. In addition, prior studies have aggregated different types of stress, categorizing them into high- and low-stress groups (Q. Wei et al., 2022), or have separated them to investigate their associations with offspring gut microbiota (Galley et al., 2023). The interactions among these various types of stress and their combined effects on the outcomes of offspring remain largely unknown (Monk et al., 2019).
One potential issue is that maternal stress is highly heterogeneous (Walsh et al., 2019). Treating it homogeneously may make examining its impact on offspring ineffective, as individual experiences can vary significantly. Latent class analysis (LCA) disentangles heterogeneity by identifying distinct patterns of maternal stress and grouping individuals according to maternal stress patterns (Nylund-Gibson and Choi, 2018). This allows for control for the effects of all stress-related measurements by using a single categorized subgroup variable derived from LCA (Chen et al., 2022). This control is essential because the specific combinations of maternal stress are likely to play a vital role in shaping offspring gut microbiota in response to adversity (Monk et al., 2019).
The primary aim of the current study was to identify latent classes based on indices of maternal stress and investigate the association between stress patterns and infant gut microbiota from a life course perspective. An infant's initial intestinal secretions can directly indicate their in-utero environment conditions, in contrast to their gut microbiota during later periods. Meconium, which initially colonizes the infant's intestinal tract, is less influenced by the postnatal environment (Ahanya et al., 2005). Therefore, this study used meconium samples collected within 48 h of birth to assess newborn infant gut microbiota.
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