METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.
RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.
INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.
METHODS: A systematic review on ischemic stroke was carried out for all articles obtained from databases until 22nd October 2020. Main findings were extracted from all the eligible studies.
RESULTS: Eighteen eligible studies were included in the systematic review. These studies suggested that aging, inflammation, and different microbial compositions could contribute to ischemic stroke. Phyla Firmicutes and Bacteroidetes also appeared to manipulate post-stroke outcome. The important role of microbiota-derived short-chain fatty acids and trimethylamine N-oxide in ischemic stroke were also highlighted.
CONCLUSIONS: This is the first systematic review that investigates the relationship between microbiome and ischemic stroke. Aging and inflammation contribute to differential microbial compositions and predispose individuals to ischemic stroke.