Ischemic Stroke Shifts the Protein and Metabolite Profiles of Colon in Mice

Abstract

Over half of all stroke patients present gastrointestinal complications. It has been speculated that there is an intriguing brain-gut connection. However, molecular mechanisms of the connection remain poorly illuminated. Thus, this study is aimed to investigate molecular alternations regarding proteins and metabolites in the colon upon ischemic stroke using multi-omics analyses. Here, stroke mouse model was induced by means of transient middle cerebral artery occlusion. After the confirmation of successful model evaluated as evidenced by neurological deficit and cerebral blood flow decrease, the proteins and metabolites of colon and brain were respectively measured using multiple omics. Functional analysis of differentially expressed proteins (DEPs) and differential metabolites was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. There were 434 common DEPs in the colon and brain after stroke. The DEPs in the two tissues displayed common enrichment in several pathways upon GO/KEGG analyses. The common KEGG pathways of DEPs were mainly linked to the inflammation and immune network. Although there was no common differential metabolite and its corresponding pathway in the two tissues, several metabolism pathways in the colon were also changed after stroke. In conclusion, we have demonstrated that the proteins and metabolites in the colon are significantly changed after ischemic stroke, which provides molecular-level evidence regarding the brain-gut connection. In this light, several common enriched pathways of DEPs may become potential therapeutic targets for stroke upon the brain-gut axis. Notably, we have discovered a promising colon-derived metabolite enterolactone possibly beneficial for tackling stroke.