Effect of Prenatal and Postnatal Stress in Rats on the Gut Microbiome in Adolescence

Previous research suggests that early-life stress (ELS) increases the risk of mental health disorders later in life. It is hypothesised that ELS disrupts the developing gut microbiome, which in turn may alter neuroendocrine and immune system development, thereby increasing disease susceptibility. However, the specific microbial taxa and pathways mediating these effects remain poorly characterised. Here, we used rat models to investigate whether ELS leads to long-term alterations in the gut microbiome. Microbial composition was assessed using 16S rRNA Nanopore sequencing of DNA extracted from faecal pellets of adolescent male and female rats exposed to: (i) early postnatal dexamethasone (DEXA; a synthetic glucocorticoid) or saline control, (ii) prenatal stress (PRS) and controls, or (iii) postnatal stress (POS) and controls. Microbiome structure was evaluated using richness, evenness, dominance and diversity indices. We show that ELS induces model-specific and sex-dependent changes in gut microbiome composition, primarily at the level of overall community structure rather than individual taxa. DEXA exposure produced the most consistent compositional signature, particularly in males, whereas PRS showed minimal detectable effects and POS exhibited a more heterogeneous response characterised by increased dispersion and limited taxonomic shifts. More broadly, these findings demonstrate that integrating beta-diversity analyses with machine learning approaches can identify reproducible microbiome patterns associated with ELS, even in the absence of large taxonomic changes. Applying similar frameworks in larger and longitudinal cohorts will be important to determine how these subtle microbial signatures contribute to long-term physiological outcomes.