Potential Inflammatory Biomarkers and Differential Gut Microbiota in Cognitive Impairment After Ischemic Stroke

Lishuo Wu,1,2,* Yajie Jiang,3,* Wei Xu,2 Liwen Wang,2 Liping Li,2 Chunli Zhang,1 Keyu Huang,1 Yi Yang,2 Jian Dai,2 Fengkun Zhou1 1Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, People’s Republic of China; 2Department of Psychological and Sleep Rehabilitation,Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 3Engineering Research Center of Innovative Traditional Chinese, Zhuang and Yao Materia Medica, Ministry of Education, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengkun Zhou, Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, People’s Republic of China, Email [email protected] Jian Dai, Department of Psychological and Sleep Rehabilitation,Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China, Email [email protected]: Ischemic stroke, one of the main public health problems worldwide, causes a variety of physiological dysfunction, including cognitive impairment. Although studies have been focused on posted-stroke cognitive impairment (PSCI), its pathological mechanism remains unclear.Methods: Here, we enrolled 66 participants stratified into three groups: healthy controls (HC, n=15), post-stroke patients without cognitive impairment (PSWCI, n=15), and PSCI patients (n=36). We analyzed clinical parameters and changes of several cytokines and gut microbiota profiles.Results: We found that compared with healthy control (HC) group, levels of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), homocysteine (Hcy), CRP and IL-6 were significantly increased in PSWCI and PSCI patients. Of them, levels of Hcy and IL-6 in PSCI group were significantly higher than that in PSWCI. ROC curve analysis identified Hcy and IL-6 as potential diagnostic biomarkers for PSCI. Furthermore, 16S rRNA sequencing of gut microbiota shows that the abundance of blaut, bifidobacterium and macromonas increased, while the abundance of bacteroides and bifidobacterium brevis decreased significantly.Conclusion: These findings suggest that elevated Hcy and IL-6 levels may serve as risk factors for PSCI, with gut microbiota dysregulation potentially contributing to its pathogenesis.Keywords: post-stroke cognitive impairment, IL-6, homocysteine, diagnostic efficacy, gut microbiota