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. 2023 Oct 13;15(20):4365. doi: 10.3390/nu15204365

Table 1.

Summary of included studies (see Supplementary Material S4 for complete data extraction table).

Study Year Location Population Size Age Gender Sample Type Matching Factor Sample
Preservative
Extraction Method Sequencing Platform Sequenced Regions Forward Primer Reverse Primer Data
Availability
Main Microbiota Finding
[38] 2019 Finland 128 (64 case, 64 control) case: 65.2 ± 5.52/control: 64.45 ± 6.9; (years, mean ±SD) Female: case: 48.6%/control: 50.0% stool age, sex DNA stabilizer PSP (Spin Stool DNA Plus Kit, STRATEC Molecular) PSP Spin Stool DNA Plus Kit (STRATEC Molecular) Illumina MiSeq V3–V4 341F1–4 (5′ CCTACGGGNGGCWGCAG 3′) 785R1–4 (5′ GACTACHVGGGTATCTAATCC 3′) PRJEB27564 Significant differences in gut microbiota between cases and controls. Disease progression did not influence gut microbiota. No difference in Firmicutes/Bacteroidetes ratio between cases and controls.
[39] 2020 Ireland 309 (147 case, 162 control) case: 69.3 ± 8.6/control: 63.3 ± 8.3; (mean ± SD) Female: case: 31.5%/control: 35.8% stool age, sex MNIgene.GUT® kit Chemagic DNA blood protocol Illumina MiSeq V3–V4 NR NR Available on request Composition of the gut microbiome could potentially serve as a marker of disease severity in PD. Bilophila and Paraprevotella abundance were significantly associated with disease severity.
[23] 2018 Italy 350 (237 cases, 113 control) cases: 67.6 (9.7)/control: 65.9 (9.9); (y, mean (SD)) cases: 115 (59.6)/control 47 (41.6): Male gender, n (%) stool age, nutritional status, geographical area No preservative QIAamp DNA Stool Mini Kit Illumina MiSeq V3–V4 NR NR NR Low Lachnospiraceae in cases.
[19] 2017 Germany 59 (31 case, 28 control) case: 64.8 ± 9.5/control 65.6 ± 10.4; (years, mean ± SD) Male: all case and control stool age NR NR Illumina Hiseq4000 NR NR NR ERP019674 Case and controls had different gut microbiota composition, characterized by increased levels of Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, and decreased levels of Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) in cases.
[44] 2020 Canada 300 (197 case, 103 control) case:66 (59–71)/control 66 (58–71); (years) Female: case: 38.1%/control: 51.5% feces age DNA stabilizer buffer OMNIgeneGUT Kit Illumina MiSeq V4 515F 806R On publisher’s website Increased abundance of Akkermansia and Bifidobacterium and decreased abundance of Faecalibacterium, Lachnospiraceae, and SCFA-producing bacteria in cases.
[22] 2020 Germany 101 (71 case, 30 control) case: 65.3 ± 10.2/controls: 64.3 ± 8.9; (years) Female: case 45.7%/controls: 45.2% feces MS score, NMS constipation item, Wexner Constipation, coffee consumption DNA stabilizing solution PSP R Spin Stool DNA Plus Kit Illumina MiSeq V3–V4 341F (5′-ACTCCTACGGGAGGCAGCAG-3′) 806R (5′-GGACTAC HVGGGTWTCTAAT-3′) Available on request High abundance of Faecalibacterium, Ruminococcus, Clostridia, Lachnospiraceae, Oscillospira, Betaproteaobacteria, Burkholderiales, Alcaligenaceae, and Sutterella in cases compared to controls.
[20] 2017 Germany 154 (76 case, 78 control) case: 68.0 6 9.7/control: 68.4 6 6.7; (year) Male: case 66%/control 59% stool diabetes medication Stool specimen collector (MedAuxil) Qiagen AllPrep kit Illumina MiSeq V4 515F 805R PRJNA381395 High abundance of Akkermansia in PD, different gut microbiota between cases and controls.
[24] 2017 USA 327 (197 case, 130 control) Total 69, 68.4, 9.2; (Median, Mean, SD) Female: 65; 132 (67.0%), Male (% Male) stool PD medications, disease duration, spousal relationship, geographic site Media-free swabs kit with DNA/RNA-free sterile swabs According to the Earth Microbiome Project Protocol Illumina MiSeq V4 515F 806R ERP016332 Significantly higher abundance of Bifidobacteriaceae, Christensenellaceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families in cases compared to controls/association of a high abundance of Akkermansia, Lactobacillus, Bifidobacterium, and reduced Lachnospiraceae (chain fatty acids producer) with disease development.
[41] 2017 Germany 58 (29 case, 29 control) case: 69.2, 6.5/control: 69.4, 6.7 (years; mean, SD) case: 23 male, 6 female/control: 13 male, 16 female stool age Shipment with no preservative, at room temp PowerSoil Kit Illumina MiSeq V1–V2 NR NR NR High abundance of Lactobacillaceae, Barnesiellaceae, and Enterococcacea in cases.
[14] 2015 USA 72 (38 case, 34 control) case: 61.6 ± 9.4/control: 45.1 ± 14.4; (mean) case: 24/14, control: 18/16; male/female fecal samples and sigmoid mucosal biopsies NR Supporting info Supporting info NR V4 NR NR NR Anti-inflammatory butyrate- producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in the feces of controls than PD patients/Faecalibacterium were significantly more abundant in the mucosa of controls than in PD/proinflammatory bacteria such as Proteobacteria were significantly more abundant in the mucosa of PD than controls/the ratio of Firmicutes-to-Bacteroidetes in fecal samples was not significantly different between PD and HC groups/positive correlation of Bacteroidetes and Proteobacteria with PD duration/negative correlation of Firmicutes with PD duration.
[47] 2019 China 99 (51 case, 48 control) case: 62.4 ± 8.2, control: 62.2 ± 9.2 (years, mean ± SD) case: male: 32, female: 19/control: control: male: 19, female: 29 stool age Sterilized tube QIAamp Fast DNA Stool Mini Kit HiSeq2500 PE250 V4 515F 806R NR Low alpha and beta diversity, high abundance of Akkermansia, P. copri Prevotella, Ruminococcaceae, Veillonellaceae Verrucomicrobiaceae, methanobrevibacter smithii, Ruminococcus callidus, Roseburia inulinivorans, Parabacteroides merde, Ruminococcus torques in cases and a high abundance of Bacteroidales, Lactobacillaceae, lactobacillus gasseri in controls.
[21] 2019 China 20 (10 case, 10 control) over 65 case: male: 7 (70%)/control: male: 5 (50%) feces NR DNA/RNA Shield PSP SPIN Stool DNA plus kit Illumina MiSeq V1–V3 341F 805R NR Slightly different gut microbiota between cases and controls, a significant abundance of Bacteroides and Prevotellaceae in healthy controls, a significant abundance of Ruminococcaceae, Verrucomicrobiaceae, Porphyromondaceae, Hydrogenoanaerobacterium, and Lachnospiraceae in PD cases.
[27] 2018 China 120 (75 case, 45 control) case: 60.48 ± 10.72/control; 63.20 ± 6.00 case: male: 49, female: 26/control: male: 23, female: 22 stool age Without preservation solution at room temperature during shipment Huirui.® DNA kit Illumina HiSeq PE250 V4 V4T9 (5′-GTGTGYCAGCMG-CCGCGG TAA-3′) V4R19 (5′-CCGGACTACNVGGGTWTCTAAT-3′) NR Significant reductions in Tenericutes, Euryarchaeota, and Firmicutes, Lachnospiraceae in patients with PD. Veillonellaceae and Verrucomicrobiaceae showed marked increases but without statistical significance. Significant differences in alpha diversity (but not beta) between patients with PD who had a disease duration of greater than 5 years compared to those with a disease duration of fewer than 5 years.
[49] 2019 Taiwan 157 (80 case, 77 control) case: 62.3 ± 7.8/control: 61.8 ± 8.3 case: 62.5% men/control: 60% men stool age and sex Flash-frozen on dry ice, and stored at −80 °C QIAamp Fast DNA Stool Mini Kit Illumina MiSeq V3–V4 NR NR NR Microbiota from patients with PD dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores.
[48] 2017 China 38 (24 case, 14 control) case: 73.75 ± 6.26/control: 74.64 ± 5.57 case: 16 men/control: 6 men stool age and sex NR TIANamp stool DNA kit (Tiangen Biotech Co., Ltd., Beijing, China) Illumina MiSeq V3–V5 5′-CCTACGGRRBGCASCAGKVRVGAAT-3′ e 5′-GGACTACNVGGGTWTCTAATCC-3′ NR The genera Blautia, Faecalibacterium, and Ruminococcus were significantly decreased in PD compared to healthy controls. The genera Escherichia-Shigella, Streptococcus, Proteus, and Enterococcus were significantly increased in PD subjects.
[50] 2017 Russia 155 (89 case, 66 control) case: 67/control: 63 NR stool age and sex NR NR Illumina MiSeq V3–V4 NR NR NR Reduction in taxonomic diversity of gut microbiota in patients with PD.
[51] 2019 Italy 152 (80 case, 72 control) NR NR stool age, sex, loss of weight NR PSP Spin Stool DNA Kit Plus (Stratec Molecular) Illumina MiSeq V3–V4 NR NR PRJNA510730 Significantly higher levels of Lactobacillaceae, Enterobacteriaceae, and Enterococcaceae families compared to healthy individuals. On the other hand, the levels of Lachnospiraceae were significantly reduced in PD patients.
[52] 2020 China 80 (40 case, 40 control) case: 66.6 ± 7.1/control: 66.3 ± 8.1 case: 19 men/control: 21 men stool lifestyle, gender, age, and BMI NR QIAamp DNA Stool Mini Kit (Qiagen) Illumina HiSeq X-ten NR NR NR PRJNA433459 The diversity and community of gut microbial genes in PD patients differed from those of healthy control subjects. Thirty-six different taxa were enriched in the PD patients, and no taxon was enriched in the healthy controls.
[53] 2018 China 90 (45 case, 45 control) case: 68.1 ± 8.0/control: 67.9 ± 8.0 case: 22 men/control: 23 men stool age, sex, BMI, constipation NR QIAamp DNA Stool Mini Kit (Qiagen) Illumina MiSeq V3–V4 341F 806R PRJNA391524 Some bacteria were correlated with PD clinical characteristics, including disease duration, severity, medication, and non-motor symptoms.
[66] 2020 China 40 (27 case, 13 control) case: 62.1 ± 10.2/control: 63 ± 8.76 case: 19 men/control: 3 men stool age NR QIAamp DNA Stool Mini Kit (Qiagen) Illumina MiSeq V3–V4 515F 5′-GTGCCAGCMGCCGCGGTAA-3′ 926R 5′-CCGTCAATTCMTTTGAGTTT-3′ PRJNA561023 Compared with HC and patients with PD-NC, the gut microbiota of patients with PD-MCI was significantly altered, particularly manifesting in enriched genera from Porphyromonadaceae family and decreased abundance of genera Blautia and Ruminococcus.
[55] 2021 Malaysia 200 (104 case, 96 control) case: 65.4 ± 8.4/control: 62.4 ± 9.0 case: 62.5% male/control: 37.5% male stool age, sex Preservatives were not added QIAamp DNA Stool Mini Kit (Qiagen) Illumina MiSeq V3–V4 341F (5′-CCTACGGGNGGCWGCAG-3′) 805R (5′-GACTACHVGGGTATCTAATCC-3′) PRJNA494620 Ten bacterial taxa were significantly increased in PD; largest fold changes were observed for B. fragilis, Lactobacillus acidophilus, Megasphaera and Gammaproteobacteria.
[56] 2020 Italy 115 (64 case, 51 control) case: 71.39 ± 10.99/51.67 ± 12.42 case: 44 men/control: 31 men stool sex, age, BMI, coffee consumption, smoking NR QIAamp DNA Stool Mini Kit (Qiagen) Illumina MiSeq V3–V4 NR NR PRJEB30401 The most significant changes within the PD group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia.
[43] 2019 Germany 59 (34 case, 25 control) case: 67.9 ± 8.6/63.9 ± 5.8 case: 23 men/control: 11 men stool age Sterile containers FastDNA SPIN kit Illumina MiSeq V4–V5 520 F (5′-AYTGGGYDTAAAGNG-3′) 926 R (5′-CCGTCAATTCMTTTRAGTTT-3′) PRJEB30615 PD patients exhibit alterations in their gut microbiota composition, characterized by a decrease in beneficial bacteria and an increase in certain bacterial groups. A potential link between the gut microbiome and PD development, as well as the influence of PD medications on the gut microbiota.
[60] 2021 China 40 (20 case, 20 control) case: 63.65 ± 5.64/61.95 ± 4.73 case: 10 men/control: 10 men stool age, sex, BMI NR DNeasy PowerSoil Kit (Qiagen) Illumina MiSeq V3–V4 343 F: 5′-TACGGRAGGCAGCAG-3′ 798 R: 5′-AGGGTATCTAATCCT-3′ NR A greater abundance of Alistipes, Rikenellaceae_RC9_gut_group, Bifidobacterium, Parabacteroides, while Faecalibacterium was decreased in fecal samples from PD patients.
[62] 2020 China 126 (63 case, 63 control) case: 64.0 ± 7.4/63.9 ± 7.9 case: 40 men/control: 23 men stool age NR QIAamp Fast DNA Stool Mini Kit (Qiagen) Illumina HiSeq PE250 V4 NR NR CRA001938 There were markedly different microbial compositions among PD, HS, and HP samples by alpha/beta diversity. They also found differential microbial compositions among Hoehn and Yahr stage/disease duration.
[25] 2014 Finland 144 (72 case, 72 control) case: 65.3 ± 6 5.5/64.5 ± 6.9 case: 51.4% male/control: 50% men stool age, sex NR NR NR V1–V3 NR NR NR Reduced abundance of Prevotellaceae in PD patients and the positive association of Enterobacteriaceae abundance with PIGD symptoms.
[40] 2022 China 172 (132 case (mild: 43, moderate: 89), 40 control) 60 to 90 M/F case: 15/28 (mild AD), 33/56 (moderate AD)/control: 16/24 feces age, sex Special cytoprotective agent E.Z.N.A. Soil DNA Kit Illumina MiSeq V3–V4 CCTACGGGNGGCWGCAG GACTACHVGGGTATCTAATCC PRJNA855571 Elevated abundance of certain bacteria in cases (moderate vs. control), including Proteobacteria, Verrucomicrobia, Actinobacteria, and Synergistetes. Reduced levels of Firmicutes and Bacteroidetes in cases. Controls, when compared to mild and moderate cases, showed higher levels of Firmicutes, Erysipelotrichia, Acidaminococcaceae, Ruminococcaceae, and Bacteroidetes.
[26] 2022 Canada 99 (45 case, 54 control) case: 74: (65–78)/control: 70 (66–74); (year) Female: case 33.3%/control 33.3% feces age OMNIgene® GUT QIAamp PowerFecal DNA Kits MiSeq V4 515F (GTGCCAGC MGCCGCGGTAA) 806R (GGACTACHVHHHTWTCTAAT) PRJNA770746 No significant different between AD patients and controls (beta diversity), lower alpha diversity in cases, higher abundance of Erysipelotrichaceae in cases.
[45] 2021 China 64 (28 cases (18 AD), 18 control) case: 63.5 (4.7)/control: 64.5 (4.5); (SD) Male (%): case 2 (11)/control: 4 (22) feces age, sex NR PowerSoil DNA Isolation Kit Illumina Miseq/Microseq V3–V4 NR NR NR AD cases exhibited increased microbial diversity, decreased levels of Bacteroides, Lachnospira, and Ruminiclostridium, and increased Prevotella.
[17] 2019 USA 108 case: 84.7 (8.1)/control: 83 (10.2); (mean [SD]) (year) Male: case: 4 (16.7)/control: 8 (15.7) stool age, sex NR PowerMag soil DNA isolation kit NextSeq 500 NR NR NR Upon request Significant increase in Bacteroides, Alistipes, Odoribacter, Barnesiella, Osplanchnicus, Odoribacter spp., K. pneumoniae, B. fragilis, E. lenta, and Desulfovibrio AD (sulfate-reducing bacteria). Conversely, there were significant decreases in bacteria, including Lachnoclostridium, Butyrivibrio, B. proteoclasticus, B. hungatei, Eubacterium, E. eligens, E. hallii, E. rectale, Clostridium sp. SY8519, R. hominis, and F. prausnitzii./significantly different beta diversity between controls and AD cases.
[46] 2022 Kazakhstan 84 (41 case, 43 control) case: 68 (62–74)/control 68 (61–75); (median (IQR)) Female, n (%): case 30 (73.2%)/control 35 (81.4%) feces NR special kit QIAamp DNA stool Mini Kit Illumina MiSeq NR NR NR PRJNA811324 Increased abundance of Acidobacteriota, Verrucomicrobiota, Planctomycetota, and Synergistota and decreased abundance of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus in AD patients.
[28] 2019 China 97 (33 case (32 aMCI), 32 control) case: 74.85 ± 11.37 (AD), 70.53 ± 11.0 (aMCI)/control: 76.88 ± 9.35; (years, mean ± SD) Male: case: 14 (AD; 42.42%), 18 (56.25%) aMCI/control 16 (50%) feces age, sex Sterile collection containers QIAGEN Illumina MiSeq V3–V4 5′-CAAGCAGAAG ACGGCATACGAGATGTGACTGGAGTTCAGACGTGTGCTCTTCCGA TCT-3′ 5′-AATGATACGGCGACCACCGAGATC TACACTCTTTCCCTACACGACGCTCTTCCGATCT-3′ PRJNA496408 Decreased diversity in AD patients compared to controls. Different gut microbiota between healthy and cases/reduced abundance of Firmicutes, increased abundance of Proteobacteria in cases/a significant correlation between AD severity and the abundance of altered microbiomes/association of Enterobacteriaceae with AD.
[42] 2021 China 105 (case: 53 (SCD) 14 (CI: MCI, n = 8; mild AD dementia, n = 6))/38 control) case: 66.68 ± 6.32 (SCD), 73.21 ± 7.89 (CI)/control: 66.79 ± 5.13; (year) M/F: case: 10/43 (SCD), 4/10 (CI)/control: 15/23 feces age, sex, educational years, other potential factors Cytoprotective agents QIAamp DNA Stool Mini Kit Illumina Miseq PE250 V3–V4 341F (CCTAC GGGRSGCAGCAG) 806R (GGACTACVVGGGTATCTAATC) NR Decreasing abundance of Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, and Faecalibacterium in cases.
[54] 2020 Austria 41 (23 case, 18 control) case: 88 (73, 85)/control: 75 (74, 76); (years) F/M: case: 15/18, control: 11/7 stool age, sex Collection tubes MagnaPure LC DNA Isolation Kit III Illumina MiSeq V1–V2 27F (AGAGTT TGATCCTGGCTCAG) R357 (CTGCTGCCTYCCGTA) PRJNA608281 Decreased abundance of Lachnospiraceae in cases, clear clustering of case and controls at different stages of dementia according to beta diversity, AD association with a reduction in bacteria producing short-chain fatty acids (SCFA) and increased biomarkers of gut permeability and inflammation. Increased abundance of C. clostridioforme and Eisenbergiella is associated with cognitive impairment.
[18] 2022 Spain 22 (12 case, 10 control) 60 to 70 case: 2 men/control: 6 men stool NR NR QIAamp PowerFecal Pro DNA isolation kit (Qiagen, Madrid, Spain) Illumina MiSeq NR 515F-Y (50 GTG YCA GCM GCC GCG GTA A 30 806R (50 GGA CTA CNV GGG TWT CTA AT 30 NR At a more advanced stage of AD, the gut microbiota and volatiles shifted towards a profile with increases in Ruminococcus and Blautia.
[58] 2022 Thailand 40 (20 case, 20 control) case: 72.8 ± 5.6/control: 69.4 ± 6.2 case: 45.5% male/control: 38.5% male stool NR Preservation System (Norgen Biotek Corp., Thorold, ON, Canada) QIAamp Stool Mini kit (Qiagen, USA) Illumina MiSeq V3–V4 NR NR NR A significant difference at the operational taxonomic unit level. The altered gut microbiome could be potentially targeted for the early diagnosis of dementia and the reduction in AD risk.
[59] 2021 China 65 (21 case, 44 control) case: 76.2 ± 9.9/control: 78.4 ± 6.6 case: 13 men/control: 20 men stool NR Sterile fecal collection containers E.Z.N.A.@ Stool DNA Kit (Omega Bio-Tek, Norcross, GA, USA) Illumina Miseq V3–V4 338 forward (5′-ACTCCTACGGGAGGCAGCAG-3′) 806 reverse (5′-GGACTACHVGGGTWTCTAAT-3′) SRP252374 Gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD. Fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.
[61] 2022 Turkey 98 (47 case, 51 control) case: 71.4 ± 5.1/control: 67 ± 5.3 case: 24 men/control: 28 men stool NR NR QiaAmp DNA stool minikit (Qiagen, Germany) Illumina MiSeq V3–V4 341 F (59-CCTACGGGNGGCWGCAG-39) 805 R (59-GACTACHVGGGTATCTAATCC-39) NCBI BioProject database A different gut microbiota composition in AD cases marked primarily by Prevotella and Bacteroides, but also subnetworks of other taxa exist in the community.
[63] 2021 China 92 (60 case, 32 control) case: 72.82 ± 7.25/control: 71.06 ± 5.92 case: 24 men/control: 14 men stool age NR QIAamp® DNA Stool Mini Kit (Qiagen, Hilden, Germany) Illumina MiSeq V3–V4 5-CCTACGGGNGGCWGCAG-3 5-GACTACHVGGGTATCTAATCC-3 NR AD patients had gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains.
[65] 2018 China 86 (43 case, 43 control) case: 70.12 ± 8.76/control: 69.72 ± 9.24 case: 23 men/control: 23 men stool age, sex NR QIAamp® DNA Stool Mini Kit (Qiagen, Hilden, Germany) Illumina MiSeq V3–V4 338F 806R NR Altered gut microbiota composition and diversity AD cases compared to cognitively normal controls. Several bacterial taxa, including Actinobacteria, Bacteroidales, Ruminococcaceae, Selenomonadales, and Lachnoclostridium, were found to contribute to these differences.
[64] 2022 China 302 (125 MCI, 83 AD case, 94 control) case: 71.8 ± 8.3/control: 74.3 ± 10.6 case: 53 men/control: 58 men stool NR Sterile containers E.Z.N.A.® soil DNA Kit (Omega Bio-tek, Norcross, GA, USA) Illumina MiSeq V3–V4 338F (50 -ACTCCTACGGGAGGCAGCAG-30) 806R (50-GGACTACHV GGGTWTCTAAT-30) NR No significant difference in the alpha and beta diversity among groups. Patients with AD or MCI had increased bacterial taxa including Erysipelatoclostridiaceae, Erysipelotrichales, Patescibacteria, Saccharimonadales, and Saccharimonadia, compared with NC group.
[57] 2017 USA 50 (25 case, 25 control) case: 71.3 ± 7.3/control: 69.3 ± 7.5 case: 8 men/control: 7 men stool age, sex NR NR Illumina MiSeq V4 NR NR NR Decreased microbial diversity in AD cases and compositionally distinct from controls.