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. 2023 Jun 13;15(2):750–763. doi: 10.3390/neurolint15020047

Table 4.

Region 2—Germany, Ireland, and Finland.

Author/Country/Year * Sample Number Methodology Microbiota Alteration in PD Mechanisms (Theories) Association Limitations
Hopfner et al., 2017, Germany [23]. Cases: (n = 29)
Controls: (n = 29)
Samples: Next-generation sequencing of the 16S rRNA gene. - Significant increase in PD patients of Family: Lactobacillaceae
- Higher abundance in PD cases of:
Family: Barnesiellaceae.
The GI microbiome influences the enteric nervous system and through the vagal nerve reaches the central nervous system. Yes - Previous dietary habits, also cardiovascular comorbidities were present in the control group.
- Cases were using PD treatment.
Heintz-buschart et al., 2017, Germany [24]. ** Cases: (n = 99)
Controls: (n = 76)
Samples: 16S and 18S ribosomal RNA amplicon sequencing from flash-frozen stool and nasal swab. - Relative abundances in the PD patients of: Genus: Akkermansia Family: Verrucomicrobiaceae
- In addition, 75% showed the same changes in the gut microbiome between the PD patients and RBD vs. the HC: Genus: Anaerotruncus, Clostridium XIVb. Phylum: Bacteroidetes.
Akkermansia spp. abundance is related to higher susceptibility to a pathogen due to the depletion of the mucus layer. Yes - Comorbidity of diabetes and coronary artery disease were found to affect the prokaryotic taxonomic profiles.
- Oral intake of diabetes medication was considered a potential confounder.
Hertel et al., 2019, Ireland [25]. Cases: (n = 30)
Controls: (n = 30)
- Targeted metabolomic analysis.
- Computational analysis methods and the Virtual Metabolic Human database.
- Significant increase in abundance of: Genus: Akkermansia muciniphila and Bilophila wadsworthia. A. muciniphila produces hydrogen sulfide, which is pro-inflammatory and harmful to the gut. This correlates to gastrointestinal motility dysfunction and higher absorption of bacterial toxins through the gut barrier in PD patients. B. Wadsworthia produces sulfite, which is pro-inflammatory to the gut and a neurotoxin. Yes - The effects of exercise were not monitored.
- The study results could be influenced by dietary variance.
- The study results cannot describe the mechanics involved in PD presentation and metabolic alterations.
Aho et al., 2019, Finland [26]. Cases: (n = 64)
Controls: (n = 64)
Stool samples: twice on average 2–2.5 years apart: 16s rRNA gene amplicon sequencing. - Increased in fecal samples in PD patients at baseline and follow-up: Genus: Bifidobacterium, Lactobacillus, Roseburia—progressed PD patients had a Firmicutes-dominated enterotype.
- Less abundant in PD patients and faster progression patients: Genus: Prevotella.
The early nonmotor symptoms of PD led to the hypothesis that it could originate outside the CNS, in the enteric nervous system. Yes - Deficient follow-up.
- PD intake medication
stroke or TIA was common among the controls.

* Case–control studies; cases were PD patients. ** Cases included PD patients (n = 78) and RBD patients (n = 21). PD: Parkinson’s disease; GI: gastrointestinal; RBD: REM sleep behavior disorder; HC: healthy controls; CNS: central nervous system; TIA: transient ischemic attack.