Abstract:
OBJECTIVE:Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. 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.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Tan AH,Chong CW,Lim SY,Yap IKS,Teh CSJ,Loke MF,Song SL,Tan JY,Ang BH,Tan YQ,Kho MT,Bowman J,Mahadeva S,Yong HS,Lang AEdoi
10.1002/ana.25982subject
Has Abstractpub_date
2020-12-03 00:00:00eissn
0364-5134issn
1531-8249pub_type
杂志文章abstract::Three-dimensional (volume) magnetic resonance angiography is a noninvasive technique that images the intracranial and cervical arterial vasculature without contrast agents. Twenty-four children with strokes had combined parenchymal magnetic resonance imaging and magnetic resonance angiography 1 day to 4 years after ac...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290603
更新日期:1991-06-01 00:00:00
abstract::The clinical and neuropathological findings in 28 cases of paramedian thalamic and midbrain infarcts are reported. The 4 instances of unilateral paramedian thalamic infarct were characterized by mood and behavioral changes, limitation of the infarct to the center of the anatomical paramedian territory, and symmetrical...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410100204
更新日期:1981-08-01 00:00:00
abstract::Juvenile myoclonic epilepsy is a common type of idiopathic generalized epilepsy characterized by myoclonic, generalized tonic-clonic, and in 30% of patients, absence seizures. We studied a three-generation pedigree of 33 members, 10 of whom were clinically affected with juvenile myoclonic epilepsy or presented with su...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390208
更新日期:1996-02-01 00:00:00
abstract::Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(200101)49:1<114::aid-ana18>3.0.c
更新日期:2001-01-01 00:00:00
abstract::To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes fro...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24314
更新日期:2015-02-01 00:00:00
abstract::Patients with the acquired immunodeficiency syndrome (AIDS) commonly display evidence of gross cerebral atrophy, but its true incidence and pathophysiology in the general AIDS population are unknown. In this study, we measured cerebrospinal fluid (CSF) spaces in 64 consecutively autopsied patients with AIDS, compared ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320107
更新日期:1992-07-01 00:00:00
abstract::One of the most striking manifestations of Down's syndrome is profound mental retardation. Furthermore, after 35 years of age, many patients with Down's syndrome develop clinical and pathological features of Alzheimer's disease. Since brains of patients with Alzheimer's disease show significant loss of neurons in the ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410180306
更新日期:1985-09-01 00:00:00
abstract::Charcot-Marie-Tooth (CMT) neuropathies are inherited neuromuscular disorders caused by a length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are causative of the neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The inc...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.23987
更新日期:2013-09-01 00:00:00
abstract::This report describes, for what may be only the second time, a ruptured miliary aneurysm within a cerebral hemorrhage. The report is unique in that the aneurysm has arisen at the site of a dissection within the wall of an arteriole at a site of fibrinoid necrosis. The case not only is a unique illustration of this pat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10664
更新日期:2003-09-01 00:00:00
abstract::Averaged electroencephalographic activity related to rhythmic jerking movements was recorded in a patient with a complex neurological symptomatology. The diagnosis of a functional disorder was strongly suggested by his clinical course, inconsistent findings from physical examination, and negative workup. His abnormal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200614
更新日期:1986-12-01 00:00:00
abstract::We here report the second and third mutations in alphaB-crystallin causing myofibrillar myopathy. Two patients had adult-onset muscle weakness. Patient 1 had cervical, limb girdle, and respiratory muscle weakness and died of respiratory failure. Patient 2 had proximal and distal leg muscle weakness. Both had myopathic...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10767
更新日期:2003-12-01 00:00:00
abstract::Although the cause of multiple sclerosis (MS) has remained obscure, many findings support an autoimmune pathogenesis on the background of a complex interaction between multiple genes and environmental factors. Accordingly, targeting the immune system has been a rational approach for the treatment of MS. The developmen...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21289
更新日期:2007-10-01 00:00:00
abstract:OBJECTIVE:Predicting hemorrhagic transformation (HT) is critical in the setting of recanalization therapy for acute stroke. Dedicated magnetic resonance imaging (MRI) sequences for detection of increased blood-brain barrier (BBB) permeability recently have been developed. We evaluated the ability of a novel MRI permeab...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21174
更新日期:2007-08-01 00:00:00
abstract::Patients are understandably anxious if seizures occur immediately after temporal lobectomy. Such "neighborhood" seizures are commonly regarded as irrelevant to seizure outcome and discounted in outcome measurement. We conducted an in-depth examination of early postoperative seizures (<28 days) and outcome. The risk of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20372
更新日期:2005-02-01 00:00:00
abstract::The effect of focal ischemia on tissue pH was studied at various times up to 6 hours after permanent middle cerebral artery occlusion in rats. Tissue pH was imaged by using umbelliferone fluorescence and correlated with cerebral blood flow, ATP content, and recordings of the steady potential. Circumscribed foci of all...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::The regional metabolic rate for glucose (rMRglu) was studied in macaque monkeys after spinal cord transection at T10, both during spinal shock and after reflexes had returned. The rMRglu was measured in all Rexed layers in cord segments both caudal and rostral to the level of the transection utilizing the quantitative...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140106
更新日期:1983-07-01 00:00:00
abstract::The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050212
更新日期:1979-02-01 00:00:00
abstract::Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients di...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050310
更新日期:1979-03-01 00:00:00
abstract::We studied 21 patients with complex partial seizures during phenobarbital (PB) or primidone withdrawal. Blood levels were measured daily, and seizure frequency was monitored by nursing staff and EEG-video telemetry. Patients were monitored for one week of baseline and for five weeks after PB tapering was initiated (wi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220515
更新日期:1987-11-01 00:00:00
abstract::We describe the clinical and oculographic findings in 4 families with episodic ataxia and interictal nystagmus (EA-2) linked to chromosome 19p. Episodes varied from pure ataxia to combinations of symptoms suggesting involvement of the cerebellum, brainstem, and cortex. Some affected individuals exhibited a progressive...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410105
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association. METHODS:Subjects were 436 well-character...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22520
更新日期:2011-11-01 00:00:00
abstract::Epileptic patients experienced an irreversible loss of their peripheral visual field upon treatment with vigabatrin (gamma-vinyl GABA), an inhibitor of the GABA degrading enzyme, GABA transaminase. Subsequently, central visual function was reported to also be irreversibly altered. This visual loss is associated with a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20081
更新日期:2004-05-01 00:00:00
abstract::The genetic analysis of simple Mendelian epilepsies remains a key strategy in advancing our understanding of epilepsy. In this article, we describe a new family epilepsy syndrome, partial epilepsy with pericentral spikes, which we map to chromosome 4p15. We distinguish it clinically, electrophysiologically, and geneti...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10221
更新日期:2002-06-01 00:00:00
abstract::A 56-year-old man was seen with subacute cerebellar degeneration and was found to have oat cell carcinoma of the lung. Antibodies to cerebellar Purkinje cells and granule cells were detected in both serum and cerebrospinal fluid (CSF), and intrathecal antibody synthesis was suggested by serum CSF antibody ratios, CSF ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410190117
更新日期:1986-01-01 00:00:00
abstract::Dopa-responsive dystonia (DRD) is one form of childhood-onset idiopathic torsion dystonia. Adult-onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320502
更新日期:1992-11-01 00:00:00
abstract::The fate of neurofilament (NF) proteins was examined in sections of nerves from rats that survived for 3 to 90 days following nerve transection, using anti-NF monoclonal antibodies and immunohistochemical techniques. The same methods were also applied to twenty-three human nerve biopsy specimens. Granular debris with ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160312
更新日期:1984-09-01 00:00:00
abstract::Intraneural perineuriomas are benign peripheral nerve sheath tumors that cause progressive debilitating focal extremity weakness. The etiology of perineuriomas is largely unknown. We utilized whole exome sequencing, copy number algorithm evaluation, and high-resolution whole genome microarray to investigate for a gene...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24854
更新日期:2017-02-01 00:00:00
abstract::To evaluate the proportion of cases of myoglobinuria that can be ascribed to specific metabolic defects, we have studied eight enzymes--phosphorylase, phosphorylase kinase, phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), lactate dehydrogenase (LDH), carnitine palmitoyltransfer...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410270214
更新日期:1990-02-01 00:00:00
abstract::Association studies have implicated common variants in the 12q14.1 region containing CYP27B1 in multiple sclerosis (MS). Rare CYP27B1 mutations cause autosomal recessive vitamin D-dependent rickets type 1, and it has recently been reported that heterozygous CYP27B1 mutations are associated with increased MS susceptibi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23834
更新日期:2013-03-01 00:00:00
abstract::A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. We analy...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400420
更新日期:1996-10-01 00:00:00