Background: Alterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established.Methods: A total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3–V4 region) sequencing. Microbiota comparisons were made between groups with good outcome (n = 105) and poor outcome (n = 27) based on 3-month modified Rankin Scale scores of 0–2 and 3–6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).Results: Patients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, p = 0.025; Simpson index, p = 0.010), an increase in the pathogenic bacteria (e.g., Enterococcaceae and Enterococcus), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., Bacteroidaceae, Ruminococcaceae, and Faecalibacterium) to those with good outcome group (all p < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome (p < 0.05).Conclusion: This study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.

Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats.

Stroke induces disorder of gut microbiota, however, whether this disorder differs according to stroke severity and its role in the evolution and outcome of stroke is currently unknown. Here we explored the composition and structure of fecal microbiome based on 68 acute ischemic stroke patients presenting with minor symptoms (admission National Institute of Health Stroke Scale (NIHSS) ≤ 3) and 67 patients with non-minor stroke (admission NIHSS 4-34) using high-throughput Illumina sequencing of the 16S rRNA. There was no significant difference in α-diversity indices, but the principal coordinate analysis of the microbiota indicated clear separation of the two groups. The significantly enriched butyrate-producing genus Roseburia in the minor stroke group was negatively correlated with fasting glucose, while the Erysipelotrichaceae incertae sedis abundant in non-minor stroke patients was positively correlated with stress hyperglycemia (i.e. fasting glucose/glycated hemoglobin ratio). Moreover, the relative abundance of genus Roseburia was also significantly associated with the dynamic changes of NIHSS score, as well as short-term and long-term functional outcomes. Our results suggested that stroke affects microbiota composition in a manner differentiated by stroke severity, and the enrichment of genus Roseburia may play a protective role in stroke evolution and outcome. Our findings strengthen the relevance of specific taxa for stroke severity that might allow targeted therapy in acute ischemic stroke.

Aging-related neurocognitive disorder (NCD) is a growing health concern. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from dietary precursors, might emerge as a promising biomarker of cognitive dysfunction within the context of brain aging and NCD. TMAO may increase among older adults, Alzheimer’s disease patients, and individuals with cognitive sequelae of stroke. Higher circulating TMAO would make them more vulnerable to age- and NCD-related cognitive decline, via mechanisms such as promoting neuroinflammation and oxidative stress, and reducing synaptic plasticity and function. However, these observations are contrary to the cognitive benefit reported for TMAO through its positive effects on blood–brain barrier integrity, as well as from the supplementation of TMAO precursors. Hence, current disputable evidence does not allow definite conclusions as to whether TMAO could serve as a critical target for cognitive health. This article provides a comprehensive overview of TMAO documented thus far on cognitive change due to aging and NCD.

Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. Prevotella histicola is a species of Prevotella, belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of Prevotella histicola on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + Prevotella histicola group. The VaD rats (the 2VO group and 2VO + Prevotella histicola group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ Prevotella histicola group were administered with Prevotella histicola twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + Prevotella histicola group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of Prevotella histicola may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, Prevotella histicola attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of Prevotella histicola transplantation as a promising treatment of VaD.