Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa-carbidopa intrajejunal gel
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Melis M, Vascellari S, Santoru ML, Oppo V, Fabbri M, Sarchioto M, Murgia D, Zibetti M, Lopiano L, Serra A, Palmas V, Pisanu S, Perra D, Madau V, Cusano R, Uva P, Mereu A, Contu P, Morelli M, Atzori L, Melis M, Manzin A, Cossu G
Journal
European journal of neurology
Year
2021
Keywords:
LCIG, Parkinson, duodopa, levodopa, microbiota
BACKGROUND AND PURPOSE: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. METHODS: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. RESULTS: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. CONCLUSIONS: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.
Experiment 1
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Subjects
- Location of subjects
- Italy
- 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
- Parkinson's disease IDIOPATHIC PARKINSON DIS,Idiopathic Parkinson Disease,Idiopathic Parkinson's Disease,IDIOPATHIC PARKINSONS DIS,Idiopathic PD,LEWY BODY PARKINSON DIS,Lewy Body Parkinson Disease,Lewy Body Parkinson's Disease,Paralysis agitans,paralysis agitans,PARKINSON DIS,PARKINSON DIS IDIOPATHIC,Parkinson disease,Parkinson Disease, Idiopathic,Parkinson syndrome,Parkinson's,Parkinson's disease,Parkinson's disease (disorder),Parkinson's disease NOS,Parkinson's disease NOS (disorder),Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinson's syndrome,Parkinsonian disorder,Parkinsonism, Primary,Parkinsons,PARKINSONS DIS,PARKINSONS DIS IDIOPATHIC,PARKINSONS DIS LEWY BODY,Parkinsons disease,Primary Parkinsonism,parkinson's disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Naive
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Levodopa (LD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Parkinson’s Disease patients treated with Levodopa (LD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 23
- Group 1 sample size Number of subjects in the case (exposed) group
- 46
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3A
Description: LEfSE comparison between Levodopa (LD) and Naive groups showing significantly enriched taxa
Abundance in Group 1: increased abundance in Levodopa (LD)
| NCBI | Quality Control | Links |
|---|---|---|
| Collinsella | ||
| Collinsella aerofaciens | ||
| Erysipelothrix muris |
Revision editor(s): Anne-mariesharp, Ese
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3A
Description: LEfSE comparison between Levodopa (LD) and Naive groups showing significantly enriched taxa
Abundance in Group 1: decreased abundance in Levodopa (LD)
Revision editor(s): Anne-mariesharp, Ese
Experiment 2
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- LD-carbidopa intestinal gel (LCIG)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Parkinson’s Disease patients treated with Levodopa-carbidopa intestinal gel (LCIG)
- Group 1 sample size Number of subjects in the case (exposed) group
- 38
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3B
Description: LEfSE comparison between LD-carbidopa intestinal gel (LCIG) and Naive groups showing significantly enriched taxa
Abundance in Group 1: increased abundance in LD-carbidopa intestinal gel (LCIG)
Revision editor(s): Anne-mariesharp, Ese
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3B
Description: LEfSE comparison between LD-carbidopa intestinal gel (LCIG) and Naive groups showing significantly enriched taxa
Abundance in Group 1: decreased abundance in LD-carbidopa intestinal gel (LCIG)
Revision editor(s): Anne-mariesharp, Ese
Experiment 3
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Levodopa (LD)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Levodopa-carbidopa intestinal gel (LCIG)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 46
Lab analysis
Statistical Analysis
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
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3C
Description: LEfSE comparison between Levodopa-carbidopa intestinal gel (LCIG) and Levodopa (LD) groups showing significantly enriched taxa
Abundance in Group 1: increased abundance in Levodopa-carbidopa intestinal gel (LCIG)
Revision editor(s): Anne-mariesharp, Ese
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Figure 3C
Description: LEfSE comparison between Levodopa-carbidopa intestinal gel (LCIG) and Levodopa (LD) groups showing significantly enriched taxa
Abundance in Group 1: decreased abundance in Levodopa-carbidopa intestinal gel (LCIG)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Blautia hansenii | ||
| Clostridiaceae | ||
| Lachnospira | ||
| Lactobacillaceae | ||
| Lactobacillus | ||
| Peptostreptococcaceae | ||
| Sedimentibacter | ||
| Tindallia |
Revision editor(s): Anne-mariesharp, Ese
Experiment 4
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- Linear Regression
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, diet, physical activity, sex, smoking status, constipation, Confounders controlled for: "coffee consumption" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.coffee consumption, Confounders controlled for: "phenotype" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.phenotype, Confounders controlled for: "disease duration" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.disease duration, Confounders controlled for: "UPDRS-III scale" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.UPDRS-III scale, Confounders controlled for: "UPDRS-IV scale" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.UPDRS-IV scale, Confounders controlled for: "oil consumption" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.oil consumption, Confounders controlled for: "supplement" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.supplement, Confounders controlled for: "balanced nutrition" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.balanced nutrition, Confounders controlled for: "Non-Motor Symptom Scale (NMSS)" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Non-Motor Symptom Scale (NMSS)
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
Reviewed Marked as Reviewed by KateRasheed on 2025-4-29
Source: Table 2
Description: Multivariate Analysis differences of gut microbiota in LCIG-Group vs LD-Group
Abundance in Group 1: increased abundance in Levodopa-carbidopa intestinal gel (LCIG)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Escherichia | ||
| Serratia |
Revision editor(s): Anne-mariesharp
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