Propionic acid (PA), a short-chain fatty acid and a metabolite of the gut microbiome, plays a significant role in health but has been associated with various pathologies, including autism spectrum disorder (ASD). Experimental studies in rodents have shown that elevated levels of PA can induce molecular and immune changes similar to those observed in ASD (MacFabe, et al.). However, limited knowledge exists regarding its impact on brain structural integrity. In this study, we examined the effects of a single intraperitoneal injection of PA at a dose of 175 mg/kg on adolescent male Wistar rats. Specifically, we focused on the central nucleus of the amygdala, a region crucial for emotional processing and implicated in ASD pathology. Structural analyses were performed at 5, 10, and 15 days post-treatment. Our findings indicate that even at this relatively low dose, PA administration resulted in a rapid reduction in amygdala neuron density and an increase in glial cell populations within 5 days. Ultrastructural analysis at 10 days post-treatment revealed moderate yet numerous synaptic pathologies, some of which persisted irreversibly. Morphometric examination further highlighted alterations in synaptic parameters, including pronounced changes in mitochondrial structure and distribution. These results support the hypothesis that PA exposure may serve as a mechanism through which the gut microbiome dynamically influences emotional processing and synaptic architecture. The research was funded by PHDF-21-2891 from the Shota Rustaveli National Science Foundation, Georgia.