Abstract DP200: Taurine Supplementation Modulates Gut Microbiome and Enhances Stroke Recovery in Aged Mice

Background: Taurine has been identified as a potential neuroprotective agent due to its potent antioxidant and anti-inflammatory properties. We found that delayed taurine supplementation after stroke decreased post-stroke depression (PSD) phenotypes seen in aged male mice, and this was independent of changes in infarct size. However, the mechanisms by which taurine contributes to post-stroke recovery remain elusive. Here, we investigated the effects of taurine in mice both male and female mice subjected to stroke. Hypothesis: We hypothesized that aged mice treated with taurine will have changes in microbial composition in the gut and changes in intestinal immune responses after stroke, and reduced PSD-like behavior compared to vehicle-treated mice. Methods: Aged C57BL/6 male and female mice (16-18 months) were subjected to a transient 60-minute middle cerebral artery occlusion. At 72h post-surgery mice were randomly assigned to one of two groups: 1). Taurine supplementation (in drinking water) or 2). Vehicle (drinking water without taurine). Neurologic deficit scores (NDS) and behavioral testing was performed at baseline and at regular intervals until euthanasia on post-stroke day 42. Flow cytometry was used to examine immune changes in the brain, blood, and spleen. 16S rRNA gene sequencing was used to determine changes in the gut microbiome composition. Results: Aged mice treated with taurine after stroke had significant reductions in stroke-induced weight loss (n=10/grp) compared to mice that received vehicle treatment (n=11/grp; p<0.05). Taurine treated mice demonstrated improved NDS (p<0.05) and higher grooming time in the sucrose splash test, indicative of reduced PSD (p<0.05). Flow cytometry of gut tissue shows a reduction of stroke-associated cytotoxic T lymphocytes and increased B lymphocyte counts in taurine treated group compared to vehicle (**p<0.01 n=16,18). 16S rRNA sequencing revealed taurine increased Enterocloster, a beneficial microbial genus, while depleting Bacteroides species (p<0.05). Conclusion: Our results demonstrates that post-stroke taurine supplementation significantly changes the gut microbiome composition in parallel to enhancing overall recovery in aged mice. Although changes in gut microbiome appears to be a key contributor to taurine induced recovery, more studies are needed to further elucidate the underlying mechanisms before potentially translating taurine into a potential therapeutic strategy for adult stroke survivors.