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

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-5-29

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

35463646

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2022.837019

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022099/

Authors

Fu SC, Lee CH, Hsieh YC, Wu PH, Lin SH, Wang H

Journal

Frontiers in cellular and infection microbiology

Year

2022

Keywords:

Parkinson’s disease, constipation, drowsiness, entacapone, levodopa, microbiome

BACKGROUND AND AIMS: Entacapone, one of the most common drugs distributed among patients with Parkinson's disease, is a peripherally acting catechol-O-methyltransferase (COMT) inhibitor that is used in addition to levodopa to control symptoms. However, there have been negative effects reported against entacapone, namely, gastrointestinal (GI) problems and drowsiness. In this pilot study, we aim to examine the hypothesis that the discomfort induced by entacapone might be originated from the shift of microbial composition by adjusting the effect of levodopa. METHODS: The population in this pilot study consisted of 13 PD patients treated with levodopa only and 11 with both levodopa and entacapone. The 16S rRNA gene sequence data were processed, aligned, and categorized using the DADA2. Alpha diversity indices for Observed, Chao1, Shannon, and Simpson metrics were calculated with Phyloseq 1.32.0. Dissimilarities were calculated using unweighted unique fraction metrics (Unifrac), weighted Unifrac, and Canberra distance. Functional differences were calculated by PICRUSt2 based on the KEGG database. RESULTS: Results of 16S rRNA sequencing analysis showed that while entacapone did not influence the species richness, the composition of the microbial community shifted considerably. Relative abundances of bacteria related to constipation and other GI disorders also altered significantly. Functional enrichment analysis revealed changes in the metabolic activity of alanine, aspartate, and glutamate. These amino acids are related to common side effects of entacapone such as auditory hallucinations, fatigue, and nightmare. CONCLUSION: Our findings provide testable hypothesis on the cause of unpleasant side effects of entacapone, which in the long run could possibly be reduced through gut microbiota manipulation.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-5-29

Curated date: 2024/04/06

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Scholastica

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Clinical treatment Clinical treatment,clinical treatment

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Parkinson's disease (PD) patients treated with levodopa only (PD_L)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Parkinson's disease (PD) patients treated with both levodopa and Entacapone (PD_LE)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Parkinson's disease (PD) patients treated with both levodopa and Entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor that is used in addition to levodopa to control symptoms.

Group 0 sample size Number of subjects in the control (unexposed) group: 13

Group 1 sample size Number of subjects in the case (exposed) group: 11

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): None

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4-V5

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Ion Torrent

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: T-Test

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Richness Number of species: unchanged

Signature 1

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Curated date: 2024/04/09

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Scholastica

Source: Figure 3, text

Description: Genera significantly different in abundance in Parkinson's disease patients treated with levodopa only (PD_L) versus Parkinson's disease (PD) patients treated with both levodopa and Entacapone (PD_LE).

Abundance in Group 1: increased abundance in Parkinson's disease (PD) patients treated with both levodopa and Entacapone (PD_LE)

NCBI	Quality Control	Links
Bifidobacterium
Eubacterium
Christensenellaceae R-7 groupChristensenellaceae R-7 group

Revision editor(s): Fiddyhamma, Scholastica

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2024-5-29

Curated date: 2024/04/09

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Scholastica

Source: Figure 3, text

Description: Genera significantly different in abundance in Parkinson's disease patients treated with levodopa only (PD_L) versus Parkinson's disease (PD) patients treated with both levodopa and Entacapone (PD_LE).

Abundance in Group 1: decreased abundance in Parkinson's disease (PD) patients treated with both levodopa and Entacapone (PD_LE)

NCBI	Quality Control	Links
Blautia
Dorea
Faecalibacterium
Intestinibacter
Lactobacillus
Sellimonas

Revision editor(s): Fiddyhamma, Scholastica