Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson’s Disease

Kessel, Sebastiaan P. van; Aidy, Sahar El

doi:10.3233/jpd-191780

Cited by 33 publications

(40 citation statements)

References 96 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 In our study, its abundance was decreased in PD + MA mice. In addition, van Kessel and El demonstrated that decreased abundance of Lachnospiraceae in PD patients was reported in six studies, 34 which is in total agreement with our study. Another study revealed that the abundance of Ruminococcaceae was significantly heightened in PD patients, 35 which contrasted with our results.…”

Section: Discussionsupporting

confidence: 53%

Electroacupuncture may alleviate behavioral defects via modulation of gut microbiota in a mouse model of Parkinson’s disease

Han

et al. 2021

Acupunct Med

View full text Add to dashboard Cite

Objective: Parkinson’s disease (PD) is a chronic neurodegenerative disease involving non-motor symptoms, of which gastrointestinal disorders are the most common. In light of recent results, intestinal dysfunction may be involved in the pathogenesis of PD. Electroacupuncture (EA) has shown potential effects, although the underlying mechanism remains mostly unknown. We speculated that EA could relieve the behavioral defects of PD, and that this effect would be associated with modulation of the gut microbiota. Methods: Mice were randomly divided into three groups: control, PD + MA (manual acupuncture), and PD + EA. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used to establish the mouse model of PD. Rotarod performance tests, open field tests, and pole tests were carried out to assess motor deficiencies. Immunohistochemistry was conducted to examine the survival of dopaminergic neurons. 16S ribosomal RNA (rRNA) gene sequencing was applied to investigate the alterations of the gut microbiome. Quantitative real-time polymerase chain reaction (PCR) was performed to characterize the messenger RNA (mRNA) levels of pro-inflammatory and anti-inflammatory cytokines. Results: We found that EA was able to alleviate the behavioral defects in the rotarod performance test and pole test, and partially rescue the significant loss of dopaminergic neurons in the substantia nigra (SN) chemically induced by MPTP in mice. Moreover, the PD + MA mice showed a tendency toward decreased intestinal microbial alpha diversity, while EA significantly reversed it. The abundance of Erysipelotrichaceae was significantly increased in PD + MA mice, and the alteration was also reversed by EA. In addition, the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were substantially increased in the SN of PD + MA mice, an effect that was reversed by EA. Conclusion: These results suggest that EA may alleviate behavioral defects via modulation of gut microbiota and suppression of inflammation in the SN of mice with PD, which provides new insights into the pathogenesis of PD and its treatment.

show abstract

Section: Discussionsupporting

confidence: 53%

Electroacupuncture may alleviate behavioral defects via modulation of gut microbiota in a mouse model of Parkinson’s disease

Han

et al. 2021

Acupunct Med

View full text Add to dashboard Cite

show abstract

“…Abnormalities in the composition and distribution of intestinal bacteria have been suggested in PD patients [ 57 ]. It has been postulated that α-synuclein pathology may spread from gut to the brain and contribute to PD etiology, however, the exact mechanism remains unclear [ 13 ]. The microbiota-derived metabolites provide a functional readout of the microbiome and can indicate the metabolic interplay among the host, diet, and intestinal bacteria [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry

Shao

Liu

et al. 2021

Mol Neurodegeneration

View full text Add to dashboard Cite

Background Parkinson’s disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future.

show abstract

“…Consequently, changes in the appendix microbiome may have a widespread effect on the microbiota of the intestine, which may be reflected in changes in stool microbiota. Furthermore, inflammation in the periphery and the brain has been proposed to have a central role in PD, and the microbiome and the host immune system have a bidirectional effectual relationship [ 12 , 21 , 22 ]. Microbiota can modify inflammatory responses and immunity in the gut, and the lymphoid tissue of the appendix is particularly relevant since it is especially rich in lymphocytes compared to the rest of the GI tract [ 11 ]; microbial metabolites have direct access to the immune cells within the lymphoid follicles of the appendix [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease

Killinger

Ensink

et al. 2021

Metabolites

View full text Add to dashboard Cite

The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations. We investigated the changes in the functional microbiota in the appendix of PD patients relative to controls (n = 12 PD, 16 C) by metatranscriptomic analysis. We found microbial dysbiosis affecting lipid metabolism, including an upregulation of bacteria responsible for secondary bile acid synthesis. We then quantitatively measure changes in bile acid abundance in PD relative to the controls in the appendix (n = 15 PD, 12 C) and ileum (n = 20 PD, 20 C). Bile acid analysis in the PD appendix reveals an increase in hydrophobic and secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA). Further proteomic and transcriptomic analysis in the appendix and ileum corroborated these findings, highlighting changes in the PD gut that are consistent with a disruption in bile acid control, including alterations in mediators of cholesterol homeostasis and lipid metabolism. Microbially derived toxic bile acids are heightened in PD, which suggests biliary abnormalities may play a role in PD pathogenesis.

show abstract

Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson’s Disease

Cited by 33 publications

References 96 publications

Electroacupuncture may alleviate behavioral defects via modulation of gut microbiota in a mouse model of Parkinson’s disease

Electroacupuncture may alleviate behavioral defects via modulation of gut microbiota in a mouse model of Parkinson’s disease

Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease

Contact Info

Product

Resources

About