<p>Acute stress induces widespread physiological and biochemical changes, significantly altering gut microbial composition and function. Herein, we explore how stress-driven shifts in the gut microbiome may impact metabolic pathways involved in neurotransmission, inflammation, and gut-brain communication. The role of microbiome-derived metabolites in shaping the host stress response is discussed. Evidence suggests that acute stress disrupts microbial balance, leading to alterations in metabolite production that may influence stress-related physiological processes. These include changes in compounds that regulate gut barrier integrity, immune responses, and neural signalling. Stress also affects pathways linked to neurotransmitter synthesis and metabolism, leading to shifts that may contribute to mood disturbances and cognitive changes. Additionally, acute stress may induce epigenetic modifications that influence gene expression in stress-regulatory pathways, further shaping the host’s physiological adaptation. Understanding these complex interactions may help identify biomarkers of stress responses and inform strategies for microbiome-based therapeutic interventions. It is anticipated that gut microbiome and/or their derived metabolites as probiotics or prebiotics may serve as potential modulators of acute stress responses by acting on the gut microbiome-brain axis pathway. We discuss these changes in response to acute stress with an eye to comprehend gut-brain axis and the associated molecular mechanisms by which the gut microbiota communicates with the brain, affecting stress responses.</p>