Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.

Study objectives: To investigate the extent to which sleep quality associated with plasma Aβ levels in amnestic mild cognitive impairment (aMCI) elderly.Methods: A total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aβ were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aβ levels after adjusting potential confounders.Results: Compared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aβ₄₂ level in the aMCI group (β = 0.063, 95% CI 0.001–0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aβ₄₂/Aβ₄₀ ratio in both NC (β = 0.010, 95% CI 0.003–0.016, and p = 0.003) and aMCI groups (β = 0.012, 95% CI 0.005–0.018, and p < 0.001). The association between global PSQI score and plasma Aβ₄₂/Aβ₄₀ ratio was stronger in individuals with aMCI relative to the NC subjects (β = 0.076 vs. 0.030, p for interaction = 0.023).Conclusion: Poor sleep quality was associated with plasma Aβ₄₂ and Aβ₄₂/Aβ₄₀ ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aβ levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer’s disease.

H-type hypertension, defined as a combination of hypertension and hyperhomocysteinemia (Hhcy), is associated with atherosclerosis and, therefore, increased stroke risk. However, the role of hypertension and Hhcy in high-risk stroke populations has not been studied. The present study investigated the prevalence of H-type hypertension in a high-risk stroke population of Hainan Province, China and to assess possible joint effects between hypertension and Hhcy for increased carotid intima-media thickness (CIMT). In this community-based cross-sectional study, 959 high-risk stroke subjects (age, 65.8 ± 10.8 years; 46.6% men) were recruited from Hainan Province, China. The demographic and clinical characteristics were collected, and blood samples were obtained. Analysis of variance or chi-square tests were performed to compare variates among groups based on both homocysteine levels and blood pressure status. The associations of hypertension and Hhcy with increased CIMT were evaluated through logistic regression. The prevalence of H-type hypertension was 34.8% in this population, with a higher ratio of H-type hypertension in men than in women. Compared with the normotension and normal homocysteine subgroup, the risk of increased CIMT was significantly higher in the subgroup with hypertension and Hhcy (odds ratio [OR] = 2.639; 95% confidence interval [CI], 1.690–4.091) after adjusting for age and sex. Increased CIMT was affected by an additive synergetic interaction between Hhcy and hypertension (synergy index = 1.105). It emphasized the clinical importance of anti-hypertension and lowering Hhcy in the high-risk stroke population.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and neuroinflammation, with emerging evidence implicating gut-brain axis dysregulation in its pathogenesis. Stromal cell-derived factor-1α (SDF-1α), a chemokine with neuroprotective properties, remains underexplored as a therapeutic agent for PD. This study investigates the efficacy of intranasal SDF-1α administration in mitigating motor deficits, gastrointestinal (GI) dysfunction, and neuroinflammation, and its concurrent effects on the gut microbiota in an MPTP-induced PD mouse model. Male C57BL/6J mice were divided into vehicle, MPTP, and MPTP + SDF-1α groups. Behavioral assessments, including the rotarod test and grip strength test, demonstrated that SDF-1α significantly attenuated MPTP-induced motor impairments, including bradykinesia and coordination deficits. Immunofluorescence analysis revealed that SDF-1α restored tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra (SN), indicating robust dopaminergic neuroprotection. Furthermore, SDF-1α ameliorated GI dysfunction by reducing intestinal permeability, as measured by FITC-dextran assay, and improving gut motility, as assessed by Evans blue transit test. Mechanistically, SDF-1α suppressed nigrostriatal inflammation by reducing pro-inflammatory cytokines (IL-6, TNF-α) while elevating anti-inflammatory markers (IL-4, IL-10). Activation of astrocytes (GFAP+) in MPTP-treated mice was reduced to near-control levels following SDF-1α administration. Gut microbiota analysis via 16S rRNA sequencing revealed that SDF-1α restored both α- and β-diversity, counteracting MPTP-induced dysbiosis. Notably, SDF-1α reversed the depletion of Akkermansia, a keystone genus associated with mucosal integrity and barrier function. These findings demonstrate that intranasal SDF-1α concurrently attenuates motor and gastrointestinal deficits, nigrostriatal neuroinflammation, intestinal barrier disruption, and gut microbiota dysbiosis in the MPTP mouse model. Our study highlights the microbiota-gut-brain axis as a critical therapeutic target in PD and proposes intranasal SDF-1α delivery as a novel, non-invasive strategy warranting further mechanistic investigation.