Cold environment is associated with worse outcomes in ischemic stroke patients and the underlying gut microbial mechanism

Increasing evidence suggests that cold environment is a potential risk factor for acute ischemic stroke (AIS) and is associated with poor prognosis, however, its underlying mechanisms remain unclear. Since gut dysbiosis and AIS are causally related and cold environment can induce changes in the gut microbiota, we wondered whether cold-season-related gut dysbiosis aggravates stroke progression. In total, 101 patients with AIS were enrolled and divided into two groups: cold-season onset ischemic stroke (CIS) and non-cold-season onset ischemic stroke (NCIS). Gut microbiota composition was analyzed using 16 S rRNA gene sequencing, and signature taxa were identified via linear discriminant analysis effect size (LEfSe). Correlations between key microbial taxa and clinical parameters were assessed using Spearman rank analysis. To evaluate the potential causal role of gut microbiota in cold season stroke, fecal microbiota transplantation (FMT) was performed in mice, followed by middle cerebral artery occlusion (MCAO). The composition of gut microbiota in the CIS group significantly differed from the NCIS group. The characteristic microbiota of the CIS group was distinguished by an elevated relative abundance of Escherichia-Shigella and Enterococcus, coupled with a decreased percentage of Blautia, Eubacterium_hallii_group, Subdoligranulum, Dorea, Faecalibacterium, Ruminococcus, and Collinsella. Furthermore, Escherichia-Shigella, Enterococcus, Blautia, Eubacterium_hallii_group and Faecalibacterium showed predictive value for 3-month poor prognosis in patients. Compared with mice inoculated with the NCIS gut microbiota, mice inoculated with the CIS gut microbiota showed more severe brain damage, impaired intestinal barrier function, and higher levels of inflammatory factors after the stroke model was established. Our study indicates that cold-season-related gut dysbiosis may be linked to stroke severity and poor prognosis in AIS patients, suggesting that modulation of gut microbiota could represent a potential avenue for therapeutic intervention.