Aging is associated with progressive oxidative stress, chronic inflammation and functional deterioration across multiple organs. Increasing evidence suggests that the gut microbiota plays a pivotal role in regulating aging through the gut-brain axis and systemic immune interactions. The present study investigated the therapeutic potential of fecal microbiota transplantation (FMT) in a D-galactose-induced rat model of accelerated aging. Male rats were allocated into four experimental groups: Healthy control, D-galactose-induced aging, aging treated with FMT and aging treated with antibiotics prior to FMT. Accelerated aging was induced by intraperitoneal administration of D-galactose (150 mg/kg/day). FMT was performed using fecal microbiota obtained from healthy donor rats. Cognitive performance was assessed using the Morris Water Maze (MWM), and histopathological alterations were evaluated in the heart, hippocampus and colon using hematoxylin and eosin staining. D-galactose administration significantly impaired spatial learning and memory and induced marked pathological alterations, including myocardial edema and hemorrhage, neuronal degeneration and vacuolation in the hippocampus, and crypt disruption with inflammatory cell infiltration in the colon. FMT markedly improved behavioral performance and substantially attenuated tissue damage in all examined organs. In contrast, antibiotic pretreatment was associated with less pronounced improvement following FMT, suggesting that the recipient intestinal environment may influence the response to transplantation. These findings provide behavioral and histopathological evidence consistent with beneficial effects of FMT on several features of accelerated aging; however, direct changes in microbial composition, microbial function, and donor engraftment were not assessed.
