Abstract
This study investigates the influence of three regulators of human homeostasis-intestinal microbiota, immune profile, and circulating metabolites-on stroke severity. We conducted a study involving 33 patients with mild/moderate stroke (MS) and 32 with severe stroke (SS), all assessed during the acute phase (first 24 h). The analysis focused on microbiota composition (45 patients), serum metabolomics and inflammatory markers (20 patients). The patients with SS exhibited more pronounced insulin resistance associated with increased levels of branched-chain amino acids and their metabolites. SS patients showed an increase in inflammatory cytokines IL-6 and TNF-α, and surprisingly an increase in IL-10 and butyrate which are anti-inflammatory. SS patients also displayed a distinct microbiota profile, with statistically significant differences in β-diversity compared to the MS group, notably a higher prevalence of Pseudomonadota (formerly Proteobacteria). In summary, our data indicate that patients with SS, compared to those with MS, are characterized by a more inflammatory and insulin-resistant state, associated with three key regulators: microbiota, metabolites, and interleukins. These findings provide new insights into the regulatory components of the gut-brain axis, which could be developed into cost-effective and widely accessible therapies for SS.