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Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The causal nature of gut microbiota and cerebral small vessel disease (CSVD) is still obscure regardless of evidence supporting their observational correlations., Objectives: The primary objective of this research is to investigate the potentially pathogenic or protective causal impacts of specific gut microbiota on various neuroimaging subtypes of CSVD., Methods: We obtained the latest summary-level genome-wide databases for gut microbiota and 9 CSVD traits. The univariable and multivariable Mendelian randomization (MR) studies were conducted to examine the possible causal link between exposure and outcome. Meanwhile, we conducted sensitivity analyses sequentially, containing the heterogeneity, pleiotropy, and leave-one-out analysis. Additionally, to clarify the potential bidirectional causality, the causality from CSVD traits to the identified gut microbiota was implemented through reverse MR analysis., Results: The univariable MR analysis identified 22 genetically predicted bacterial abundances that were correlated with CSVD traits. Although conditioning on macronutrient dietary compositions, 2 suggestive relationships were retained using the multivariable MR analysis. Specifically, the class Negativicutes and order Selenomonadales exhibited a negative causal association with strictly lobar cerebral microbleeds, one neuroimaging trait of CSVD. There is insufficient evidence indicating the presence of heterogeneity and horizontal pleiotropy. Furthermore, the identified causal relationship was not driven by any single nucleotide polymorphism. The results of the reverse MR analysis did not reveal any statistically significant causality from CSVD traits to the identified gut microbiota., Conclusions: Our study indicated several suggestive causal effects from gut microbiota to different neuroimaging subtypes of CSVD. These findings provided a latent understanding of the pathogenesis of CSVD from the perspective of the gut-brain axis., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke., (© 2024. The Author(s).)

Background: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear., Materials and Methods: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome., Results: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity., Conclusions: The gut microbiome is associated with cerebral SVD., Competing Interests: Declarations of Competing Interest Dr Saji has received grants from the Grant-in-Aid for Scientific Research (C), JSPS KAKENHI (grant 20k07861), grants from the NARO Bio-oriented Technology Research Advancement Institution Project (advanced integration research for agriculture and interdisciplinary fields), grants from the Danone Institute of Japan Foundation, grants from the Honjo International Scholarship Foundation, and the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program. Dr Saji, Dr Niida, and Dr Sakurai have received research grants from the Research Funding of Longevity Sciences from the National Center for Geriatrics and Gerontology. Dr Saji, Dr Toba, and Dr Sakurai have received research funds for Comprehensive Research on Aging and Health from the Japan Agency for Medical Research and Development (AMED). Dr Tsuduki has received grants from the NARO Bio-oriented Technology Research Advancement Institution Project (advanced integration research for agriculture and interdisciplinary fields)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Cerebral microbleeds (CMBs) is a subtype of cerebral small vessel disease. Their underlying pathogenesis remains unclear. The aim of this study was to investigate the association between infectious burden (IB) and CMBs., Methods: Seven hundred and seventy-three consecutive patients who were hospitalized in the Department of Neurology in General Hospital of Western Theater Command without severe neurological symptoms were recruited and selected in this pilot cross-sectional study. CMBs were assessed using the susceptibility-weighted imaging sequence of magnetic resonance imaging. Immunoglobulin G antibodies against common pathogens, including herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), Helicobacter pylori (HP), and Borrelia burgdorferi (B. burgdorferi), were measured by commercial ELISA assays. IB was defined as a composite serologic measure of exposure to these common pathogens., Results: Patients with and without CMBs were defined as the CMBs group (n = 76) and the non-CMBs group (n = 81), respectively. IB was significantly different between the CMBs and non-CMBs groups. After adjusted for other risk factors, the increased IB was independently associated with the presence of CMBs (P = 0.031, OR = 3.00, 95% CI [1.11-8.15]). IB was significantly positively associated with the number of CMBs (Spearman ρ = 0.653, P < 0.001). The levels of serum inflammatory markers were significantly different between the CMBs and non-CMBs groups and among the categories of IB., Interpretation: IB consisting of HSV-1, HSV-2, CMV, C. pneumoniae, M. pneumoniae, EBV, HP, and B. burgdorferi was associated with CMBs. All the findings suggested that pathogen infection could be involved in the pathogenesis of CMBs., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objectives: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model., Design: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls., Setting: Research laboratory of a university hospital., Subjects: Male Wistar rats., Interventions: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions., Measurements and Main Results: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02)., Conclusions: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.

Enterotoxemia caused by Clostridium perfringens type D is an important disease of sheep and goats with a worldwide distribution. Cerebral microangiopathy is considered pathognomonic for ovine enterotoxemia and is seen in most cases of the disorder in sheep. However, these lesions are poorly described in goats. In this article, we describe the vasculocentric brain lesions in 44 cases of caprine spontaneous C. perfringens type D enterotoxemia. Only 1 goat had gross changes in the brain, which consisted of mild cerebellar coning. However, 8 of 44 (18%) cases showed microscopic brain lesions, characterized by intramural vascular proteinaceous edema, a novel and diagnostically significant finding. The precise location of the edema was better observed with periodic acid-Schiff, Gomori's, and albumin stains. Glial fibrillary acidic protein and aquaporin 4 immunostaining revealed strong immunolabeling of astrocyte foot processes surrounding microvessels. The areas of the brain most frequently affected were the cerebral cortex, corpus striatum (basal ganglia), and cerebellar peduncles, and both arterioles and venules were involved. Most of the goats of this study showed lesions in the intestine (enteritis, colitis, and typhlitis), although pulmonary congestion and edema, hydrothorax, hydropericardium, and ascites were also described. Although the intramural edema described, for the first time, in these caprine cases is useful for the diagnosis of enterotoxemia when observed, its absence cannot exclude the disease.

Background: Limited data exists about the role of Chlamydia pneumoniae elderly patients with acute ischemic stroke., Objective: To study the role of C. pneumoniae in elderly patients (age more than 65 years) with acute ischemic stroke and its impact on stroke out come., Methods: We recruited 100 elderly patients with acute ischemic stroke and 100 age and sex matched controls over a period of 2 years. IgG and IgA anti C. pneumoniae antibodies were measured by microimmunofluorescence technique in patients and controls. Good outcome was defined as a Modified Rankin score (mRS) of ≤2., Results: We found C. pneumoniae antibodies in 35% stroke patients and in 18% control subjects (p=0.01). Good out come at 90 days follow up was found in 20/35(57.1%) seropositive stroke patients compared to 37/65(56.9%) seronegative stroke patients (p=0.9)., Conclusions: C. pneumoniae antibody positivity was independently associated with ischemic stroke in elderly patients and its presence does not alter the stroke outcome., (Copyright © 2011 Elsevier B.V. All rights reserved.)