Parkinson's disease: Are gut microbes involved?
Ontology highlight
ABSTRACT:
SUBMITTER: Bhattarai Y
PROVIDER: S-EPMC8087343 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Parkinson's disease: Are gut microbes involved?
Bhattarai Yogesh Y Kashyap Purna C PC
American journal of physiology. Gastrointestinal and liver physiology 20200902 5
Similar Datasets
Project description:Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host's inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.
| S-EPMC10309029 | biostudies-literature
Project description:In the last two decades it has become clear that Parkinson's disease (PD) is associated with a plethora of gastrointestinal symptoms originating from functional and structural changes in the gut and its associated neural structures. This is of particular interest not only because such symptoms have a major impact on the quality of life of PD patients, but also since accumulating evidence suggests that in at least a subgroup of patients, these disturbances precede the motor symptoms and diagnosis of PD by years and may thus give important insights into the origin and pathogenesis of the disease. In this mini-review we attempt to concisely summarize the current knowledge after two decades of research on the gut-brain axis in PD. We focus on alpha-synuclein pathology, biomarkers, and the gut microbiota and envision the development and impact of these research areas for the two decades to come.
| S-EPMC6311363 | biostudies-other
Project description:In the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson's disease (iPD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.
2021-07-14 | GSE145814 | GEO
Project description:As the second-largest neurodegenerative disease in the world, Parkinson's disease (PD) has brought a severe economic and medical burden to our society. Growing evidence in recent years suggests that the gut microbiome may influence PD, but the exact pathogenesis of PD remains unclear. In addition, the current diagnosis of PD could be inaccurate and expensive. In this study, the largest meta-analysis currently of the gut microbiome in PD was analyzed, including 2269 samples by 16S rRNA gene and 236 samples by shotgun metagenomics, aiming to reveal the connection between PD and gut microbiome and establish a model to predict PD. The results showed that the relative abundances of potential pro-inflammatory bacteria, genes and pathways were significantly increased in PD, while potential anti-inflammatory bacteria, genes and pathways were significantly decreased. These changes may lead to a decrease in potential anti-inflammatory substances (short-chain fatty acids) and an increase in potential pro-inflammatory substances (lipopolysaccharides, hydrogen sulfide and glutamate). Notably, the results of 16S rRNA gene and shotgun metagenomic analysis have consistently identified five decreased genera (Roseburia, Faecalibacterium, Blautia, Lachnospira, and Prevotella) and five increased genera (Streptococcus, Bifidobacterium, Lactobacillus, Akkermansia, and Desulfovibrio) in PD. Furthermore, random forest models performed well for PD prediction based on 11 genera (accuracy > 80%) or 6 genes (accuracy > 90%) related to inflammation. Finally, a possible mechanism was presented to explain the pathogenesis of inflammation leading to PD. Our results provided further insights into the prediction and treatment of PD based on inflammation.
| S-EPMC9789082 | biostudies-literature
Project description:Gut Microbiome Alterations Drive Distinct Metabolic Expression Patterns in a Cohort of Italian Patients with Parkinson’s Disease
| PRJEB30401 | ENA
Project description:Parkinson's disease (PD) is a neurodegenerative disorder affecting mainly the dopaminergic neurons of the nigrostriatal pathway, a neuronal circuit involved in the control of movements, thereby the main manifestations correspond to motor impairments. The major molecular hallmark of this disease corresponds to the presence of pathological protein inclusions called Lewy bodies in the midbrain of patients, which have been extensively associated with neurotoxic effects. Importantly, different research groups have demonstrated that CD4+ T-cells infiltrate into the substantia nigra of PD patients and animal models. Moreover, several studies have consistently demonstrated that T-cell deficiency results in a strong attenuation of dopaminergic neurodegeneration in animal models of PD, thus indicating a key role of adaptive immunity in the neurodegenerative process. Recent evidence has shown that CD4+ T-cell response involved in PD patients is directed to oxidised forms of ?-synuclein, one of the main constituents of Lewy bodies. On the other hand, most PD patients present a number of non-motor manifestations. Among non-motor manifestations, gastrointestinal dysfunctions result especially important as potential early biomarkers of PD, since they are ubiquitously found among confirmed patients and occur much earlier than motor symptoms. These gastrointestinal dysfunctions include constipation and inflammation of the gut mucosa and the most distinctive pathologic features associated are the loss of neurons of the enteric nervous system and the generation of Lewy bodies in the gut. Moreover, emerging evidence has recently shown a pivotal role of gut microbiota in triggering the development of PD in genetically predisposed individuals. Of note, PD has been positively correlated with inflammatory bowel diseases, a group of disorders involving a T-cell driven inflammation of gut mucosa, which is strongly dependent in the composition of gut microbiota. Here we raised the hypothesis that T-cell driven inflammation, which mediates dopaminergic neurodegeneration in PD, is triggered in the gut mucosa. Accordingly, we discuss how structural components of commensal bacteria or how different mediators produced by gut-microbiota, including short-chain fatty acids and dopamine, may affect the behaviour of T-cells, triggering the development of T-cell responses against Lewy bodies, initially confined to the gut mucosa but later extended to the brain.
| S-EPMC6384270 | biostudies-literature
Project description:IntroductionCurrent evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis.Areas coveredIn this article, the authors review the relationship between factors such as genes and antibiotic exposure on CD onset and the intestinal microbiota. The authors also review other microbiota within the human body (like the oropharynx) that may play a role in CD pathogenesis. Finally, the authors discuss implications for disease modification and the ultimate goal of prevention. The authors reviewed literature from PubMed, EMBASE, and Web of Science.Expert opinionCD serves as a unique opportunity to explore the role of the intestinal microbiota on the development of chronic autoimmune disease. While research to date provides a solid foundation, most studies have been case-control and thus do not have capacity to explore the mechanistic role of the microbiota in CD onset. Further longitudinal studies and integrated multi-omics are necessary for investigating CD pathogenesis.
| S-EPMC7796936 | biostudies-literature
Project description:STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans and mice with STING gain-of-function mutations develop a syndrome known as STING-associated vasculopathy with onset in infancy (SAVI), which is characterized by inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of gain-of-function STING to bacterial CDNs might explain autoinflammatory lung disease in SAVI mice. We report that depletion of gut microbes with oral antibiotics (vancomycin, neomycin, and ampicillin [VNA]) nearly eliminates lung disease in SAVI mice, implying that gut microbes might promote STING-associated autoinflammation. However, we show that germ-free SAVI mice still develop severe autoinflammatory disease and that transferring gut microbiota from antibiotics-treated mice to germ-free animals eliminates lung inflammation. Depletion of anaerobes with metronidazole abolishes the protective effect of the VNA antibiotics cocktail, and recolonization with the metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming a protective role of a metronidazole-sensitive microbe in a model of SAVI.
| S-EPMC8477380 | biostudies-literature
Project description:The links between microorganisms/viruses and autoimmunity are complex and multidirectional. A huge number of studies demonstrated the triggering impact of microbes and viruses as the major environmental factors on the autoimmune and inflammatory diseases. However, growing evidences suggest that infectious agents can also play a protective role or even abrogate these processes. This protective crosstalk between microbes/viruses and us might represent a mutual beneficial equilibrium relationship between two cohabiting ecosystems. The protective pathways might involve post-translational modification of proteins, decreased intestinal permeability, Th1 to Th2 immune shift, induction of apoptosis, auto-aggressive cells relocation from the target organ, immunosuppressive extracellular vesicles and down regulation of auto-reactive cells by the microbial derived proteins. Our analysis demonstrates that the interaction of the microorganisms/viruses and celiac disease (CD) is always a set of multidirectional processes. A deeper inquiry into the CD interplay with Herpes viruses and Helicobacter pylori demonstrates that the role of these infections, suggested to be potential CD protectors, is not as controversial as for the other infectious agents. The outcome of these interactions might be due to a balance between these multidirectional processes.
| S-EPMC5539691 | biostudies-other
Project description:BackgroundThere is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD.ObjectiveThe objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research.MethodsA total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways.ResultsIndependent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation.ConclusionPD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.
| S-EPMC5469442 | biostudies-literature