Table 2.
Region 1—USA and Canada.
| Author/Country/Year * | Sample Number | Methodology | Microbiota Alteration in PD | Mechanisms (Theories) | Association | Limitations |
|---|---|---|---|---|---|---|
| Keshavarzian et al. [17], 2015, USA | Cases: (n = 38) Controls: (n = 34) |
Fecal and colonic mucosa samples: Microbial 16S rRNA gene on genomic DNA. | - Less abundant in fecal samples: Family: Lachnospiraceae Genus: Blautia, Coprococcus, Roseburia - Less abundant in mucosa samples: Family: Coprobacillaceae Genus: Dorea, Faecalibacterium - More abundant in fecal samples: Phylum: Bacteroidetes, Proteobacteria, Verrucomicrobiota Genus: Akkermansia, Oscillospira, Bacteroides - More abundant in mucosa samples: Family: Oxalobacteraceae Genus: Ralstonia. |
Family Lachnospiraceae contains several butyrate-producing bacteria, butyrate has anti-inflammatory properties. Thus, the low abundance of butyrate-producing bacteria in feces from PD subjects may be one mechanism contributing to intestinal leakiness and inflammation in PD. | Yes | Environmental factors associated with PD (age, BMI, medication use, and PD duration) might explain differences between cases and control. The study found significant differences in age between PD and controls, but its impact is uncertain. |
| Hill-Burns et al. [18], 2017, USA | Cases: (n = 197) Controls PD-household: (n = 130) |
Fecal samples: 16S rRNA amplicon sequencing on genomic DNA. | -Less abundant in fecal samples: Family: Lachnospiraceae - More abundant in fecal samples: Genus: Akkermansia, Lactobacillus, Bifidobacterium. |
SCFA are made by bacteria in the gut; notably, Lachnospiraceae is consistent with its depletion. Butyrate kinase, which catalyzes a reversible reaction between butyrate and butanoylphosphate, was reduced in PD, and acetyl-CoA synthetase, which converts acetate to acetyl-CoA, was elevated. | Yes | Most relevant potential confounders: PD medications, disease duration, marital status, and geographic site. |
| Appel-Cresswell et al. [19], 2020, Canada | Cases: (n = 95) Controls: (n = 57) |
Fecal samples: Microbial DNA was extracted using QIAGEN and amplicon base sequenced. | -Mycobiome found in fecal samples: Phylum: 86% Ascomycota,12% Basidiomycota Genus: Saccharomyces (most common 58.7%) in 94% of participants, Candida 35%, Cladosporium 23%, Penicillium 23%. | Found no correlation between PD patients and control fecal samples. | No | - Only one ITS primer pair was used for sequencing. - Additional data on environmental factors were not collected. |
| Zhang et al. [20], 2022, USA | Cases: (n = 96) Controls PD-household: (n = 74) |
Fecal samples: 16S rRNA gene sequencing, rarefaction, and feature filtering. | - More abundant in fecal samples: Phylum: Proteobacteria, Verrucomicrobiota, and Actinobacteriota. Genus: UBA1819 (Ruminococcaceae), DTU089 (Ruminococcaceae), Akkermansia, Enterococcus, and Hungatella. | Increased level of Proteobacteria has been associated with potential immunoregulation ability via the production of LPS. They initiate the immune process, stimulating microglia and leading to dopaminergic neuron necrosis. | Yes | - Gastrointestinal comorbidities. - The recent use of antibiotics was not specified. - Size, confounders control, and statistical power. - The samples were collected at a single time; this does not allow for establishing temporality or causality. - The species-level resolution of the sequencing and annotation pipeline. |
* Case–control studies; cases were PD patients. PD: Parkinson’s disease; SCFA: short-chain fatty acids; GI: gastrointestinal; ITS2: Internal transcribed spacer 2; ITS: Internal transcribed spacer; LPS: lipopolysaccharides.