Association between gut microbiota dysbiosis and poor functional outcomes in acute ischemic stroke patients with COVID-19 infection

Acute ischemic stroke (AIS) patients with active COVID-19 infection often have more severe symptoms and worse recovery. COVID-19 infection can cause gut microbiota dysbiosis, which is also a risk factor for poor outcomes in AIS patients. However, the association between gut microbiota and functional outcomes among AIS patients with COVID-19 infection has not been fully clarified yet. In this study, we performed 16S rRNA gene sequencing to characterize the gut microbial community among AIS patients with acute COVID-19 infection, AIS patients with post-acute COVID-19 infection, and AIS patients without COVID-19 infection. We found that AIS patients with acute COVID-19 experienced poorer recovery and significant gut dysbiosis, characterized by higher levels of Enterobacteriaceae and lower levels of Ruminococcaceae and Lachnospiraceae . Furthermore, a shorter time window (less than 28 days) between COVID-19 infection and stroke was identified as a risk factor for poor functional outcomes in AIS patients with COVID-19, and the enrichment of Enterobacteriaceae was indicated as a mediator in the relationship between infection time window and poor stroke outcomes. Our findings highlight the importance of early intervention after COVID-19 infection, especially by regulating the gut microbiota, which plays a role in the prognosis of AIS patients with COVID-19 infection. IMPORTANCE The gut microbiota plays an important role in the association between respiratory system and cerebrovascular system through the gut-lung axis and gut-brain axis. However, the specific connection between gut bacteria and the functional outcomes of acute ischemic stroke (AIS) patients with COVID-19 is not fully understood yet. In our study, we observed a significant decrease in bacterial diversity and shifts in the abundance of key bacterial families in AIS patients with acute COVID-19 infection. Furthermore, we identified that the time window was a critical influence factor for stroke outcomes, and the enrichment of Enterobacteriaceae acted as a mediator in the relationship between the infection time window and poor stroke outcomes. Our research provides a new perspective on the complex interplay among AIS, COVID-19 infection, and gut microbiota dysbiosis. Moreover, recognizing Enterobacteriaceae as a potential mediator of poor stroke prognosis offers a novel avenue for future exploration and therapeutic interventions.