Table 4.
Preclinical and clinical studies on the use of fecal microbiota transplantation for Parkinson’s disease.
| Ref. | Study Cohort | Study Groups | Donor | Recipient | Experimental Procedure | Results | Adverse Events |
|---|---|---|---|---|---|---|---|
| Zhao et al., 2021 [470] | Mice | Controls (n = 15), rotenone (n = 15) and rotenone + FMT (n = 15) | Control mice | Rotenone-induced PD mice | Oral gavage (100 μL bacterial suspension) daily for 2 weeks | ↓ Dysbiosis ↓ Motor symptoms ↑ Intestinal barrier and BBB integrity ↓ Systemic inflammation ↓ Neuroinflammation (SN) ↓ LPS (serum, colon and SN) ↓ TLR4/NF-κB pathway (colon and SN) |
N.A. |
| Sun et al., 2018 [469] | Mice | Controls (n = 15), MPTP + PBS (n = 15) and MPTP + FMT (n = 15) | Control mice | MPTP-induced PD mice | Gavage (200 μL bacterial suspension containing 108 CFU/mL) daily for 7 days | ↓ Dysbiosis ↓ Fecal SCFAs ↓ Motor symptoms ↑ DA and 5-HT (striatum) ↓ Microglia and astrocyte activation (SN) ↓ TLR4/TNF-α pathway (gut and brain) |
N.A. |
| Zhong et al., 2021 [471] | Mice | Controls + PBS (n = 10), controls + FMT (n = 10), MPTP + PBS (n = 10), MPTP + FMT (n = 10) | Control mice | Controls or MPTP-induced PD mice | Gavage (200 μL bacterial suspension containing 108 CFU/mL) daily for 7 days | ↓ Motor symptoms ↓ Fecal SCFAs ↓ α-syn (SN) ↓ Microglia activation (SN) ↓ TLR4/NF-κB pathway (striatum and SN) |
N.A. |
| Zhang et al., 2021 [472] | Mice | Controls (n = 3), MPTP (n = 3) and MPTP + FMT (n = 3) | Control mice | MPTP-induced PD mice | Transplantation with 200 μL bacterial suspension (containing 108 CFU/mL) daily for 2 weeks | ↓ Neuroinflammation (SN) ↓ Motor symptoms ↑ Blautia ↓ Anaerostipes, ASF356, Ruminococcus and Bifidobacterium ↓ Microglia and astrocyte activation (SN) ↓ IL-1β, iNOS, GSK3β and p-PTEN (SN) |
N.A. |
| Zhou et al., 2019 [473] | Mice | Mice pre-treated with MPTP and antibiotics, divided in PD-PBS (n = 8), PD-NA (n = 8), PD-NF (n = 8) and PD-NF/HK (n = 8) | Control mice or control mice undergoing FMT | MPTP-induced PD mice pre-treated with antibiotics | Gastric gavage (200 μL bacterial suspension containing 108 CFU/mL) daily for 7 days | ↑ DA and 5-HT (striatum) in PD-NF mice ↑ Neuroprotection in PD-NF mice |
N.A. |
| Sampson et al., 2016 [40] | Mice | GF + FMT from SPF control mice, GF + FMT from PD patients, GF + FMT from healthy patients | Human PD patients (n = 6), human healthy controls (n = 6) or SPF control mice (n = 3) | α-syn-overexpressing mice | Oral gavage | In GF + PD-FMT mice: ↑ Physical impairment ↑ Proteus, Bilophila and Roseburia ↓ Lachnospiraceae, Rikenellaceae, Peptostreptococcaceae and Butyricicoccus ↓ Acetate ↑ Proprionate and butyrate |
N.A. |
| Huang et al., 2019 [474] | Human (case report) | PD patient presenting tremor for 7 years and constipation (>3 years) | 26 y.o. healthy male | 71 y.o. male PD patients | Colonoscopy (200 mL of fecal microbiota suspension) daily for 3 days | ↓ Tremor (no tremor for 2 months) ↓ Constipation ↑ α-diversity ↓ UPDRS score 1 week after FMT |
No |
| Kuai et al., 2021 [475] | Humans (prospective single study) | PD patients | Frozen fecal microbiota from the China fmtBank | PD patients (n = 11) | Intra-intestine transplantation of 40–50 mL of frozen fecal microbiota resuspended in 200 mL saline solution | ↑ Blautia and Prevotella ↓ Bacteroidetes ↓ H-Y, UPDRS and NMSS scores ↓ Wexner constipation and PAC-QOL scores |
No |
| Xue et al., 2020 [476] | Humans | PD patients + FMT (via colonoscopy, n = 10; nasointestinally, n = 5) | 5 Healthy donors (mean 22 y.o., 3 males and 2 females) | PD patients | Colonoscopy or nasointestinal administration | ↓ PSQI, HAMA, PDQ-39, HAMD, UPDRS-III and NMSQ | 5 cases: diarrhea (n = 2), abdominal pain (n = 2) and flatulence (n = 1) |
| Segal et al., 2021 [477] | Humans (uncontrolled case series) | 6 PD patients with symptoms for 5 years (mean). | 2 healthy donors (males, 38 and 50 y.o.) | 6 PD patients with constipation (mean 52 y.o.), 3 males and 3 females | Colonoscopy (300 mL of fecal suspension) | ↓ Motor and non-motor symptoms ↓ Constipation |
1 case requiring hospitalization for observation |
Abbreviations: α-syn: α-synuclein; BBB: blood-brain barrier; CFU: colony forming units; DA: dopamine; FMD: fasting mimicking diet; FMT: fecal microbiota transplantation; GF: germ-free;GSK3β: glycogen synthase kinase-3 beta; H-Y: Hoehn and Yahr scale; HAMA: Hamilton anxiety scale; HAMD: Hamilton depression rating scale; 5-HT: serotonin;IL-1β: interleukin 1 beta; iNOS: inducible nitric oxide synthase; LPS: lipopolysaccharide; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NMSQ: non-motor symptoms questionnaire; NMSS: non-motor symptoms scale; p-PTEN: phosphorylated PTEN; PAC-QOL: patient assessment of constipation quality of life questionnaire; PBS: phosphate buffered saline; PD-NA: MPTP-induced PD mice treated receiving FMT from control mice; PD-NF: MPTP-induced PD mice treated receiving FMT from control mice undergoing FMD; PD-NF/HK: MPTP-induced PD mice treated receiving heat inactivated FMT from control mice undergoing FMD; PD-PBS: MPTP-induced PD mice treated receiving PBS; PD: Parkinson’s disease; PDQ-39: Parkinson’s Disease Questionnaire; PSQI: Pittsburgh sleep quality index; SCFAs: short chain fatty acids; SN: substantia nigra; SPF: specific pathogen free; TLR4: toll like receptor 4; TNF-α: tumor necrosis factor α; UPDRS: unified Parkinson’s disease rating scale; y.o.: years old; ↓: decrease; ↑: increase.