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Recent evidence has revealed that probiotics could affect neurodevelopment and cognitive function via regulating gut microbiota. However, the role of probiotics in sepsis-associated encephalopathy (SAE) remained unclear. This study was conducted to assess the effects and therapeutic mechanisms of probiotic Clostridium butyricum (Cb) against SAE in mice. The SAE model mouse was induced by cecal ligation and puncture (CLP) and was given by intragastric administration with Cb for 1 month. A series of behavioral tests, including neurological severity score, tail suspension test, and elevated maze test, were used to assess cognitive impairment. Nissl staining and Fluoro-Jade C (FJC) staining were used to assess neuronal injury. Microglia activation, the release of neuroinflammatory cytokines, and the levels of ionized calcium-binding adapter molecule 1 (Iba-1) and brain-derived neurotrophic factor (BDNF) in the brain were determined. The compositions of the gut microbiota were detected by 16S rRNA sequencing. Our results revealed that Cb significantly attenuated cognitive impairment and neuronal damage. Moreover, Cb significantly inhibited excessive activation of microglia, decreased Iba-1 level, and increased BDNF level in the SAE mice. In addition, Cb improved gut microbiota dysbiosis of SAE mice. These findings revealed that Cb exerted anti-inflammatory effects and improved cognitive impairment in SAE mice, and their neuroprotective mechanisms might be mediated by regulating gut microbiota.

Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has 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 3 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 non-cognitive 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.

Current IB studies focus mainly on firms’ adaptation to the technological impacts of digitalization on their internationalization activities. However, they have paid less attention to firms’ respon...

Based on resource dependence theory, our study provides a complementary view of economic perspective to understand the effect of government innovation policy on firm’s innovation in broad social co...

In this study, we address the question of why CEOs with international experience adopt a longer temporal orientation in transition economies. We propose a theoretical framework that links CEO inter...

This study integrates different research streams in the institutional literature to examine the impact of general and specific government policies on an organization’s explorative and exploitative innovation in China. Based on resource dependence theory, we argue that general government policy promotes a firm’s exploitative innovation only while specific government policy promotes explorative innovation. However, the simultaneous presence of both forms of policy can "crowd out" a general policy’s effect on a firm’s exploitative innovation efforts. The innovation norms and firm’s ownership structure can affect efforts to inspire innovation. Results based on a combination of survey and archival data collected from Chinese firms support the argument. Implications for institutional theories and the role of government in firm innovation are discussed.