The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance.
Ontology highlight
ABSTRACT:
SUBMITTER: Menozzi E
PROVIDER: S-EPMC8078923 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance.
Menozzi Elisa E Macnaughtan Jane J Schapira Anthony H V AHV
Annals of medicine 20211201 1
Gastrointestinal disorders are one of the most significant non-motor problems affecting people with Parkinson disease (PD). Pathogenetically, the gastrointestinal tract has been proposed to be the initial site of pathological changes in PD. Intestinal inflammation and alterations in the gut microbiota may contribute to initiation and progression of pathology in PD. However, the mechanisms underlying this "gut-brain" axis in PD remain unclear. PD patients can display a large variety of gastrointe ...[more]
Similar Datasets
Project description:Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (A?) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, A? has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, A? may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The A? seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.
| S-EPMC6326209 | biostudies-literature
Project description:BackgroundThe complexity of the pathogenic mechanisms underlying neurodegenerative disorders such as Parkinson's disease (PD) is attributable to multifactorial changes occurring at a molecular level, influenced by genetics and environmental interactions. However, what causes the main hallmarks of PD is not well understood. Recent data increasingly suggest that imbalances in the gut microbiome composition might trigger and/or exacerbate the progression of PD.ObjectiveThe present review aims to (1) report emerging literature showing changes in microbiota composition of PD patients compared to healthy individuals and (2) discuss how these changes may initiate and/or perpetuate PD pathology.MethodsWe analyzed 13 studies published from 2015 and included in this review. Altered microbial taxa were compiled in a detailed table summarizing bacterial changes in fecal/mucosal samples. The methodology was systematically reviewed across the articles and was also included in a table to facilitate comparisons between studies.ResultsMultiple studies found a reduction in short-chain fatty-acid-producing bacteria that can rescue neuronal damage through epigenetic mechanisms. Overall, the studies showed that changes in the gut microbiota composition might influence colonic inflammation, gut permeability, and α-synuclein aggregation, contributing to the neurogenerative process.ConclusionFurther studies with larger cohorts and high-resolution sequencing methods are required to better define gut microbiota changes in PD. Furthermore, additional longitudinal studies are required to determine the causal link between these changes and PD pathogenesis as well as to study the potential of the intestinal microbiota as a biomarker.
| S-EPMC6856467 | biostudies-literature
Project description:Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.
| S-EPMC10084001 | biostudies-literature
Project description:The gut contains the largest reservoir of microorganisms of the human body, termed as the gut microbiota which emerges as a key pathophysiological factor in health and disease. The gut microbiota has been demonstrated to influence various brain functions along the "gut-brain axis". Stroke leads to intestinal dysmotility and leakiness of the intestinal barrier which are associated with change of the gut microbiota composition and its interaction with the human host. Growing evidence over the past decade has demonstrated an important role of these post-stroke changes along the gut-brain axis to contribute to stroke pathology and be potentially druggable targets for future therapies. The impact of the gut microbiota on brain health and repair after stroke might be attributed to the diverse functions of gut bacteria in producing neuroactive compounds, modulating the host's metabolism and immune status. Therefore, a better understanding on the gut-brain axis after stroke and its integration in a broader concept of stroke pathology could open up new avenues for stroke therapy. Here, we discuss current concepts from preclinical models and human studies on the bi-directional communication along the microbiota-gut-brain axis in stroke.
| S-EPMC9673423 | biostudies-literature
Project description:Gut dysbiosis and psychiatric symptoms are common early manifestations of Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases, characterised by progressive neuron loss and pathological protein accumulation, impose debilitating effects on patients. Recently, these pathological proteins have been linked with gut dysbiosis and psychiatric disorders. The gut-brain axis links the enteric and central nervous systems, acting as a bidirectional communication pathway to influence brain function and behavior. The relationship triad between gut dysbiosis, psychiatric disorders, and neurodegeneration has been investigated in pairs; however, evidence suggests that they are all interrelated and a deeper understanding is required to unravel the nuances of neurodegenerative diseases. Therefore, this review aims to summarise the current literature on the roles of gut dysbiosis and psychiatric disorders in pathological protein-related neurodegenerative diseases. We discussed how changes in the gut environment can influence the development of psychiatric symptoms and the progression of neurodegeneration and how these features overlap in AD and PD. Moreover, research on the interplay between gut dysbiosis, psychiatric disorders, and neurodegeneration remains in its early phase. In this review, we highlighted potential therapeutic approaches aimed at mitigating gastrointestinal problems and psychiatric disorders to alter the rate of neurodegeneration. Further research to assess the molecular mechanisms underlying AD and PD pathogenesis remains crucial for developing more effective treatments and achieving earlier diagnoses. Moreover, exploring non-invasive, early preventive measures and interventions is a relatively unexplored but important avenue of research in neurodegenerative diseases.
| S-EPMC10704039 | biostudies-literature
Project description:Polyphenolic antioxidants, including dietary plant lignans, modulate the gut-brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols-some of which have enhanced blood-brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood-brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut-brain axis, focusing on AD.
| S-EPMC7074796 | biostudies-literature
Project description:BackgroundParkinson's disease (PD), characterized by the loss of dopaminergic neurons, is a progressive neurodegenerative disorder. Recent research has revealed a significant connection between gut microbiota and PD. To gain insight into research interests, disciplinary contexts, and potential future directions, a comprehensive bibliometric analysis was conducted on the brain-gut axis and PD literature published between 2014 and 2023.MethodsRelevant literature records were gathered from the Web of Science Core Collection on August 11, 2023. The data were then analyzed by Biblioshiny R packages and VOSviewer (version 1.6.19).ResultsThe dataset revealed an upward trend in annual scientific publications on the brain-gut axis and PD, with an annual growth rate of 50.24%. China, the United States, and Italy were the top three most productive countries/regions. The journal "International Journal Of Molecular Sciences" published the most articles, while "Movement Disorders" received the highest number of citations. Professor Keshavarzian A emerged as the most prolific author, while Professor Scheperjans F held the highest h-index. Keyword analysis highlighted "alpha-synuclein" as the most frequent term, with "mouse model," "inflammation," and "risk" as emerging research topics. Additionally, "central nervous system" and "intestinal bacterial overgrowth" attracted increasing attention.ConclusionThis study examined current trends and hotspots in the bibliometric landscape of the brain-gut axis and PD research. Future research directions should explore the functional and metabolic activities of gut microbiota. Additionally, transitioning from observational to interventional study designs offers the potential for personalized interventions and disease prediction. These findings can guide researchers in navigating the latest developments and shaping the future directions of this field.
| S-EPMC10954898 | biostudies-literature
Project description:The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.
| S-EPMC6304899 | biostudies-other
Project description:In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.
| S-EPMC5530613 | biostudies-other
Project description:ObjectiveThe objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD).MethodsThe authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively.ResultsCompared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group.ConclusionsThe LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.
| S-EPMC9117559 | biostudies-literature