Abstract TP085: The Gut-Brain Connection: Social Isolation and Dysbiosis in Aging

Introduction: Social isolation (SI) is psychosocial stress that worsens outcomes in multiple neurological disorders including stroke, especially in the elderly. Previous studies have shown that SI can increase systemic inflammation, cognitive decline, neuropsychiatric symptoms and metabolic disorders. Understanding the non-modifiable (e.g., genetics and age) and modifiable factors (e.g., inflammation) that regulate the pathophysiology of SI is essential for early intervention, especially prior to neurological injury. In this study, as a modifiable factor, we profiled the gut microbiota composition of isolative and interactive individuals to understand the role of gut microbiome in SI pathophysiology. Hypothesis: We hypothesize that SI impairs gut barrier function and leads to disruptions in gut microbial homeostasis (i.e., dysbiosis). This microbial imbalance may heighten local inflammation in the gut, leading to systemic inflammation and post-stroke complications such as depression and cognitive decline. Methods: We conducted whole-genome shotgun sequencing on stool samples collected from adults (both sexes) aged >50 years (N = 37) with no history of neurological disorders, to characterize the baseline gut microbiome and its functional potential. The correlational analysis of gut microbiota compositions and SI status was performed using the UCLA Loneliness Scale and the Lubben Social Network Scale. Results: SI scores were significantly positively correlated with the relative abundance of Blautia and Clostridiales (FDR-adjusted p < 0.05). In contrast, SI was negatively correlated with Phocaea and Lachnospiraceae (FDR-adjusted p < 0.05). These associations were independent of age and sex, indicating that psychosocial stress exerts effects on gut microbial composition regardless of demographic factors. Conclusion: We found a distinct microbiome signature among socially isolated individuals compared to interactive individuals, regardless of other risk factors assessed. Downstream functional analysis will help us understand how SI-induced dysbiosis can regulate neuroinflammation and cognitive health in aged individuals. Identifying these baseline microbial patterns opens the door to developing targeted microbiome-based interventions aimed at mitigating the negative impact of SI on neurological outcomes in age related diseases such as stroke.