Multi-Omics Analysis of the Gut-Brain Axis Elucidates Therapeutic Mechanisms of Guhong Injection in the Treatment of Ischemic Stroke

Guhong injection (GH) is a compound preparation widely utilized in the treatment of cerebrovascular diseases. Accumulating evidence indicates that the gut microbiota is implicated in the development of ischemic stroke (IS). However, although the therapeutic potential of GH in IS may be mediated through the gut microbiota, the intricate relationships among the gut-brain axis, biomarkers, and target proteins remain to be completely explained. A rat model of middle cerebral artery occlusion (MCAO) was utilized to investigate the impact of GH on IS. Our 16S rRNA sequence analysis revealed that GH markedly enhanced the α-diversity of the intestinal microbiome and rectified the imbalance of short-chain fatty acids (SCFAs). Metabolomic analysis indicated that GH reversed 45 biomarkers and 6 disordered metabolic pathways in MCAO rats. Among these, the metabolic pathways of arachidonic acid, α-linolenic acid, fructose, and mannose were closely associated with gut microbiota comprising Lactobacillus modulated by GH. Furthermore, IS-related signaling pathways, including inflammation, autophagy, oxidative stress, and apoptosis, were significantly associated with three gut microbial species influenced by GH. The potential efficacy of GH in the context of IS is mediated through multiple pathways, involving the gut microbiota, SCFAs, biomarkers, and target proteins. This process partly relies on the gut-brain axis.