Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke

• Published in: Frontiers in aging neuroscience Vol. 12; p. 511562
• Main Authors: Ling, Yi, Gong, Tianyu, Zhang, Junmei, Gu, Qilu, Gao, Xinxin, Weng, Xiongpeng, Liu, Jiaming, Sun, Jing
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 23.10.2020; Frontiers Media S.A
• Subjects: Abundance; Amino acids; Animal cognition; Animal models; Antibiotics; Atrophy; Bacteria; Biomarkers; Catalysts; Chaperones; Cofactors; Cognitive ability; cognitive impairment; Dementia; Dementia disorders; Deoxyribonucleic acid; Diabetes; Digestive system; DNA; Enterobacteriaceae; Feces; gut microbiome; Homocysteine; Hospitals; Hypertension; Intestinal microflora; Ischemia; ischemic stroke; Lachnospiraceae; Leukoaraiosis; Mental disorders; Microbiomes; Microbiota; Neuroscience; Pathogenesis; Patients; Probiotics; Proteobacteria; Risk factors; rRNA 16S; Schizophrenia; Stroke; Vascular dementia; Vitamins; United States > US; China
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2020.511562

Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enrolled in this study. The patients were divided into two groups according to their MoCA scores three months after stroke onset. Clinical data and biological variables were recorded. GM composition was analyzed using 16S ribosomal RNA sequencing, and the characteristic GM was identified by linear discriminant analysis Effect Size (Lefse). Our results showed that Proteobacteria was highly increased in the PSCI group compared with the post-stroke noncognitive impairment (PSNCI) group, the similar alterations were also observed at the class, order, family, and genus levels of Proteobacteria. After age adjustments, the abundance of Firmicutes, and its members, including Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other, were significantly decreased in the age-matched PSCI group compared with the PSNCI group. Besides, the GM was closely associated with MoCA scores and the risk factors for PSCI, including higher baseline National Institute of Health Stroke Scale score, higher homocysteine (Hcy) level, higher prevalence of stroke recurrence, leukoaraiosis, and brain atrophy. The KEGG results showed the enriched module for folding, sorting and degradation (chaperones and folding catalysts) and the decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in PSCI patients. A significant correlation was observed between PSCI and the abundance of Enterobacteriaceae after adjustments (P = 0.035). Moreover, the receiver operating characteristic (ROC) models based on the characteristic GM and Enterobacteriaceae could distinguish PSCI patients from PSNCI patients (area under the curve (AUC) = 0.840, 0.629, respectively). Our findings demonstrated that the characteristic GM, especially Enterobacteriaceae, might have the ability to predict PSCI in post-stroke patients, which are expected to be used as clinical biomarkers of PSCI.