IndexIntroductionPathophysiology of Parkinson's diseaseTaxonomic structure of the microbiome in Parkinson's diseaseComposition of the microbiome as a diagnostic marker for Parkinson's diseaseFunctional mechanisms proposed for the impact of the microbiome on the pathology of Parkinson's diseaseConclusionReferencesIntroductionThe disease Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell death of dopaminergic neurons and cytoplasmic aggregation of the protein alpha-synuclein. The gut microbiota has been found to play an important role in the pathology, influencing both the accumulation of Alpha Syn and the activation of microglia responsible for the inflammatory response to neuronal damage. Gastrointestinal tract (GIT) disorders represent one of the most common non-motor symptoms with 50-80% of Parkinson's disease patients exhibiting such dysfunctions. This alteration of bowel function, primarily in the form of constipation, may precede the prototypical motor symptoms of Parkinson's disease by more than a decade. There is a marked difference in the composition of gut microbial populations in Parkinson's disease patients compared to healthy controls, with the relative abundance of specific bacterial genera sufficient to distinguish between different forms of Parkinson's disease. The triggers for Parkinson's disease are currently unknown. However, environmental factors influencing primarily through the gut are likely to play a key role, most likely in a context of genetic vulnerability. This essay will discuss how gut-brain interactions influence Parkinson's disease by describing the proposed mechanisms through which the microbiome impacts its pathology. It will also explore the value of microbiota as biomarkers for early disease diagnosis and the potential of therapies to alleviate non-motor symptoms. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Pathophysiology of Parkinson's disease Parkinson's disease affects 1-3% of the population over the age of 65 and is a type of amyloidosis characterized by the cytoplasmic accumulation of α-synuclein fibrils. Despite the characterization of the disease regarding the residence of these neuropathological signs in dopaminergic neurons of the substantia nigra and striatum, there is evidence that αSyn accumulates in the gut and propagates via the vagus nerve to the brain. For example, vagotomized individuals who have part of their vagus nerve removed are at a reduced risk of Parkinson's disease. Neurons in the enteric nervous system and olfactory bulbs were also found to contain aggregated αsynuclein in patients with early Parkinson's disease. The vagal nerve is a crucial mediator of communication between the gut microbiota and the brain and refers to the pathway through which the microbiome exerts its effects on the pathology of Parkinson's disease. This affection of the ENS to the central nervous system is consistent with the clinical observation that gastrointestinal tract dysfunction sometimes precedes the motor symptoms of Parkinson's disease by years. However, the diagnostic value of the presence of these αSyn-positive aggregates in the ENS is uncertain due to their presence in healthy colon mucosa. There is debate as to whether Parkinson's disease truly begins in the gut, however, agreement is reached on the potential role of the gut microbiome in the pathology of Parkinson's disease. αsynuclein derived from exosomes of neurons in patients with ADParkinson's triggers the activation of microglia. These activated microglia are important in normal biological function and normally respond to neuronal damage by removing damaged cells via phagocytic function. However, chronic production of inflammatory products such as cytokines, reactive oxygen intermediates, proteinases, and complement proteins by microglia characterizes the slow destructive process of Parkinson's disease. There are several microbial molecules that mimic host structures and promote an immune response during the development of Parkinson's disease. The resulting loss of dopaminergic neurons leads to the cardinal motor symptoms of Parkinson's disease patients: rigidity, slowness of movement (called bradykinesia), and tremor. These symptoms progressively worsen as the disease advances. Taxonomic structure of the microbiome in Parkinson's diseaseThe human body not only has its own genome, but also hosts the genetic information of all the microorganisms that live in and with it, the so-called microbiome. Currently available studies on the microbiome of the colon, mouth and nose have shown results regarding bacterial alterations specific to Parkinson's disease, most convincingly those of the gastrointestinal tract. These studies are mainly based on the 16S rRNA gene amplification technique. The technique allows the diversity of this single ribosomal gene to be examined, enabling analysis of the genetic diversity of microbial communities. However, it could be distorted due to unequal gene expression between species leading to a distorted perception of abundance. Deeper insight into community biodiversity and microbiome function can be obtained through metagenomic sequencing, a process that allows genes from thousands of organisms to be sampled in parallel. This technique also has disadvantages related to its inability to provide sufficiently in-depth analysis to detect rare species. Overall, these techniques demonstrated that bacteria associated with an altered intestinal barrier or immune function are significantly overrepresented or underrepresented in patients with Parkinson's disease. In particular, Akkermansia and Lactobacillus increase in relative abundance, while the genera Facalibacterium and Prevotella decrease. It has not yet been established whether there is a temporal or causal relationship between the intestinal microbiota and the main characteristics of the disease. However, this dysbiosis allows Parkinson's cases to be distinguished from healthy individuals at a very early stage. A comparable microbial shift is seen in REM sleep behavior disorder, which is a risk factor for the subsequent development of synucleinopathies, including Parkinson's disease. And also it is enough to distinguish between different forms of PD. Patients with the tremor-dominant phenotype of Parkinson's disease exhibit significantly fewer Enterobacteriaceae than those with more severe postural and gait instability. A high abundance of Enterobacteriaceae is also related to a more severe PD phenotype. This accumulating evidence indicates that alterations in the human gut microbiome represent a risk factor for Parkinson's disease and correlate with disease progression. Microbiome composition as a diagnostic marker for Parkinson's disease Following these findings, the possibility of using changes in the microbiome as a marker for early diagnosis has been established. However, confounding variables that may influence the microbiome were likely responsible for the findings of the early studies, as was noted and subsequently checked.These include DNA isolation methods and experimental cohorts recruited from Parkinson's disease patients with variations in diet, age, disease stage severity, and current medications. Therefore, it is important to interpret data from these studies with caution as reproducibility and consistency may be lower. For example, a 16S rRNA amplicon sequencing study conducted in 2015 by Scheperjans and his team found that the prevotella enterotype is underrepresented in Parkinson's disease patients. The link to the pathogenesis of Parkinson's disease has been attributed to reduced mucin synthesis associated with increased intestinal permeability when prevotella levels are low. This could lead to local and systemic expression of bacterial endotoxin, an environmental trigger of Parkinson's disease, and increased expression of alpha Syn in the colon. However, in the 2017 study by Hill-Burns and colleagues involving 16S rRNA sequencing with a larger sample size (197 compared to 72) and statistical data no association between Parkinson's and the Prevotellacea family was reported .analysis included to control for potential confounders. Therefore, following suggestions such as those of the Scheperjans study to study the effects of supplementation of neuroactive chain fatty acids and the vitamins thiamine and folate to account for this deficit in the prevotella and act as a potential therapeutic in patients with Parkinson's disease could be considered premature. Other articles have also highlighted the reported inconsistencies in the influence of the prevotella genus and stated that the change in abundance may only be present in the early stages of Parkinson's disease. Attempts are now being made to standardize protocols in microbial studies to allow easier comparison of results. Proposed functional mechanisms for the impact of the microbiome on Parkinson's disease pathology Under normal conditions, Akkermansia muciniphila exerts beneficial effects on the mucosal layer of the intestine and improves the barrier function of the intestine. the intestinal epithelium. In patients with Parkinson's disease the relative abundance of this species is increased compared to normal equilibrium. This may seem counterintuitive regarding its link to the pathogenesis of Parkinson's disease; however, mucus is used as an energy source and barrier degradation could be caused if bacterial abundance is too high. Without sufficient barrier function, microbial antigens from opportunistic pathogens can activate immune cells and thus have inflammatory potential. A schematic representation of the process by which the microbiota can increase the permeability of the blood-intestinal and blood-brain barriers is found in Figure 1. The diagram is not specific to Akkermansia, however it highlights the general process by which a transmission route between the microbiota the intestine and the brain could be formed following microbial dysbiosis and the formation of induced fibrillar αsynuclein. Microbiota products such as LPS and metabolites would then be able to access the central nervous system through the compromised barriers with detrimental effects. Increased lactobacillaceae is associated with reduced levels of ghrelin, a hormone known to regulate nigrostriatal dopamine function and possibly limit neurodegeneration in the brain. PD. Lactobacilli are also thought to modulate the activity of neurons in the enteric nervous system which, as discussed above, is thought to be implicated in Parkinson's disease. This modulation can influence cellular secretion ofα-synuclein, also a hallmark of Parkinson's disease. Currently, these links are still conceptual and there is insufficient data to conclusively support them. However, Lactobacillacae levels are thought to increase in line with the progression of Parkinson's disease, indicating that this family of bacteria is somehow important to the condition. Reduced levels of Lachnaspiraceae bacteria have been reported in patients with Parkinson's disease. These bacteria produce short-chain fatty acids (SCFAs), which are microbial metabolites that play a role in Parkinson's disease. SCFA depletion is an interesting hypothesis implicated in the pathogenesis of Parkinson's disease and could potentially explain inflammation and microglial activation in the brain in addition to the gastrointestinal features of the disease. The molecules are also present in the diagram in Figure 1. There is currently little evidence of an underlying bacterial change having a significant impact on the risk of Parkinson's disease, it is more likely that changes in the complex balance of the entire microbiome are related to Parkinson's disease. Parkinson. . However, some bacteria are able to mimic host molecules that can initiate the same destructive immune response found in Parkinson's disease. The operational taxonomic unit of unclassified bacteria 469 expresses an endonuclease with a domain such as αSyn. Despite the extremely low abundance of such bacteria, it is possible that, as a consequence of specific interactions with the host, the pathophysiology of Parkinson's disease may be significantly modified. Please note: this is just a sample. Get a custom paper from our expert writers now. Personalized EssayConclusionThe link between the gut and Parkinson's disease is well established. However, characterizing the mechanisms by which the microbiome elucidates its effects has yet to be fully determined. Analysis of bacterial composition of the colon may be predictive of Parkinson's disease by allowing discrimination between its forms, but only once studies have determined the relevant biomarkers through analysis at the highest possible resolution with confounding variables adequately controlled in studies reproducible. Beyond this, a functional link between dysbiosis of particular genera comprising the microbiome and pathophysiological markers of Parkinson's disease requires further evidence. Once this is established, it may be possible to develop Parkinson's disease therapies targeting aspects of the microbiome. ReferencesAraki, K. et al., 2019. Parkinson's disease is a type of amyloidosis characterized by the accumulation of α-synuclein amyloid fibrils. Proceedings of the National Academy of Sciences of the United States of America, 3 9, 116 (36), pp. 17963-17969. Barichella, M. et al., 2019. Unraveling gut microbiota in Parkinson's Disease and atypical parkinsonism. Movement disorders, 21 3, 34(3), pp. 396-405.Bedarf, JR et al., 2019. Das Darmmikrobiom bei der Parkinson-Krankheit. Der Nervenarzt, 31 2, 90(2), pp. 160-166. Braak, H., Rüb, U., Gai, W.P. & Del Tredici, K., 2003. Idiopathic Parkinson's disease: possible pathways by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. Journal of Neural Transmission, 1 5, 110(5), pp. 517-536. Dinan, T. G. & Cryan, J. F., 2017. Gut instincts: microbiota as a key regulator of brain development, aging and neurodegeneration. The Journal of Physiology, 15 1, 595(2), pp. 489-503. Fitzgerald, E., Murphy, S. & Martinson, H.A., 2019. Pathology of alpha-synuclein and the role of the microbiota in Parkinson's disease. Frontiers in neuroscience, 24, 1. 39-48.