A Pilot Study Exploring the Association of Entacapone, Gut Microbiota, and the Subsequent Side Effects in Patients With Parkinson’s Disease

Fu, Shih-Chen; Lee, Chung-Han; Hsieh, Yi‐Chen; Wu, Pei-Hua; Lin, Sheng‐Hsuan; Wang, Hsiuying

doi:10.3389/fcimb.2022.837019

Cited by 10 publications

(9 citation statements)

References 51 publications

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“…In addition, a substantial decrease in Faecalibacterium prausnitzii abundance coupled with a trend towards lower fecal butyrate associate with entacapone, a widely prescribed COMT inhibitor [ 198 ], but not with the analogues opicapone and tolcapone (the latter one has been withdrawn from the market for safety reasons) [ 108 , 199 ]. Other studies confirmed the alteration of taxa related to GI disorders and constipation upon entacapone intake [ 185 , 200 ]. In particular, Fu et al showed reduced Sellimonas , Lactobacillus , Faecalibacterium , Dorea , Intestinobacter and Blautia as well as augmented Eubacterium , Bifodobacterium and Christensenellacea _R-7_group in PD patients receiving entacapone combined with L-dopa versus those treated with L-dopa alone [ 200 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Biomarkers And Drug ...mentioning

confidence: 56%

“…Other studies confirmed the alteration of taxa related to GI disorders and constipation upon entacapone intake [ 185 , 200 ]. In particular, Fu et al showed reduced Sellimonas , Lactobacillus , Faecalibacterium , Dorea , Intestinobacter and Blautia as well as augmented Eubacterium , Bifodobacterium and Christensenellacea _R-7_group in PD patients receiving entacapone combined with L-dopa versus those treated with L-dopa alone [ 200 ].…”

Section: Parkinson’s Disease and Gut Microbiota: Biomarkers And Drug ...mentioning

confidence: 56%

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The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Varesi¹,

Campagnoli²,

Fahmideh³

et al. 2022

IJMS

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The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.

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Section: Parkinson’s Disease and Gut Microbiota: Biomarkers And Drug ...mentioning

confidence: 56%

Section: Parkinson’s Disease and Gut Microbiota: Biomarkers And Drug ...mentioning

confidence: 56%

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Varesi¹,

Campagnoli²,

Fahmideh³

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…A sophisticated model should be adapted if microbiome and constipation status are measured repeatedly in longitudinal follow-up studies. For those types of studies, PD medications such as entacapone which potentially lead to constipation ( Fu et al., 2022 ) should be considered a candidate mediator or time-varying confounder. A comparison of the microbial alteration between the constipation versus the non-constipation groups among PD patients would also be necessary.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Causal Effect of Constipation on Parkinson’s Disease Through Mediation Analysis of Microbial Data

Shih

et al. 2022

Front. Cell. Infect. Microbiol.

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Background and AimsParkinson’s disease (PD) is a worldwide neurodegenerative disease with an increasing global burden, while constipation is an important risk factor for PD. The gastrointestinal tract had been proposed as the origin of PD in Braak’s gut–brain axis hypothesis, and there is increasing evidence indicating that intestinal microbial alteration has a role in the pathogenesis of PD. In this study, we aim to investigate the role of intestinal microbial alteration in the mechanism of constipation-related PD.MethodsWe adapted our data from Hill‐Burns et al., in which 324 participants were enrolled in the study. The 16S rRNA gene sequence data were processed, aligned, and categorized using DADA2. Mediation analysis was used to test and quantify the extent by which the intestinal microbial alteration explains the causal effect of constipation on PD incidence.ResultsWe found 18 bacterial genera and 7 species significantly different between groups of constipated and non-constipated subjects. Among these bacteria, nine genera and four species had a significant mediation effect between constipation and PD. All of them were short-chain fatty acid (SCFA)-producing bacteria that were substantially related to PD. Results from the mediation analysis showed that up to 76.56% of the effect of constipation on PD was mediated through intestinal microbial alteration.ConclusionOur findings support that gut dysbiosis plays a critical role in the pathogenesis of constipation-related PD, mostly through the decreasing of SCFA-producing bacteria, indicating that probiotics with SCFA-producing bacteria may be promising in the prevention and treatment of constipation-related PD.Limitations1) Several potential confounders that should be adjusted were not provided in the original dataset. 2) Our study was conducted based on the assumption of constipation being the etiology of PD; however, constipation and PD may mutually affect each other. 3) Further studies are necessary to explain the remaining 23.44% effect leading to PD by constipation.

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“…In particular COMT inhibitors, which have been associated with gut microbiome perturbations. 20,39 Last, the current study would benefit from other data sources, providing different types of gut microbiome profiling, including metabolomics and shotgun metagenomics for a more functional readout. Also, increased taxonomic resolution as potentially provided by shotgun metagenomics could further aid clinical trial design of probiotic studies using specific species or strains.…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic Medication Accentuates Fecal Gut Microbiome Changes in Parkinson’s Disease

Boertien

Pereira

Laine

et al. 2022

Preprint

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Fecal gut microbiota changes are associated with Parkinson's disease (PD). However, disease related changes cannot readily be discerned from medication effects, as almost all participants in previous studies were using PD medication, and conclusive longitudinal data related to treatment initiation is lacking. Here, fecal gut microbiota composition was assessed in 62 de novo PD participants who were untreated at baseline and used PD medication at one-year follow-up, by means of 16S-sequencing. In addition, participants were stratified for the type of dopaminergic medication. Overall gut microbiota composition did not differ between baseline and one-year follow-up, but was associated with levodopa dose and levodopa equivalent daily dose (LEDD). Several differentially abundant taxa are in line with previously described changes in PD. These included reduced levels of amplicon sequence variants (ASVs) belonging to Faecalibacterium prausnitzii and Lachnospiraceae in all participants at follow-up, and increased levels of an ASV belonging to Bifidobacterium in dopamine agonist users. The family Bifidobacteriaceae was increased in dopamine agonist users who only used pramipexole. Levodopa dose was inversely related to the abundance of the families Ruminococcaceae and Lachnospiraceae, and the genus Lachnospiraceae ND3007 group. PD medications exert a measurable and dose-dependent effect on gut microbiota composition and accentuate several previously described gut microbiota changes in PD. Detailed knowledge of medication effects should be part of future trial designs of gut microbiome studies in PD and are necessary to interpret previously published data.

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A Pilot Study Exploring the Association of Entacapone, Gut Microbiota, and the Subsequent Side Effects in Patients With Parkinson’s Disease

Cited by 10 publications

References 51 publications

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

Exploring the Causal Effect of Constipation on Parkinson’s Disease Through Mediation Analysis of Microbial Data

Dopaminergic Medication Accentuates Fecal Gut Microbiome Changes in Parkinson’s Disease

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