EFFACE-PD
(2026)Objective
Assess whether a single donor-derived fecal microbiota transplantation (FMT) via colonoscopy improves motor (MDS-UPDRS III OFF at 12 months) and non-motor symptoms in patients with Parkinson's disease compared with autologous-FMT placebo.
Study Summary
• MDS-UPDRS III ON was significantly better in the FMT arm at 1 month (DiD -3.5, 95% CI -5.2 to -1.8, p<0.001) but the effect was not sustained at 12 months
• Non-motor benefits favored FMT at 12 months: MDS-NMS total (DiD -20.3, p=0.03), MDS-UPDRS I (DiD -0.70, p=0.028), MDS-UPDRS II (DiD -0.7, p<0.001), GIDS-PD (DiD -4.4, p=0.003), and EQ-5D (DiD 0.03, p=0.037)
• All 36 procedure-related adverse events were transient and none were serious; no significant change in levodopa equivalent daily dose
Intervention
Single donor-derived fecal microbiota transplantation (Mbiotix HBI, 60 g stool in 200 mL saline with glycerol) delivered into the cecum via colonoscopy, after 5-day rifaximin pretreatment and bowel prep
Inclusion Criteria
Age 40-75 years; PD diagnosis per MDS clinical diagnostic criteria; on ongoing oral levodopa treatment
Study Design
Arms: Donor-derived FMT (Mbiotix HBI) via colonoscopy vs. auto-FMT placebo prepared from the patient's own stool via colonoscopy
Patients per Arm: 28 Mbiotix / 31 placebo (total N=59)
Outcome
• MDS-UPDRS III ON: DiD -3.5 (95% CI -5.2 to -1.8), p<0.001 at 1 month; not sustained (p=0.670 at 12 mo)
• MDS-NMS total at 12 mo: DiD -20.3 (95% CI -35.2 to -5.4), p=0.03 favoring FMT
• GIDS-PD at 12 mo: DiD -4.4 (95% CI -6.9 to -1.8), p=0.003 favoring FMT
• EQ-5D at 12 mo: DiD 0.03 (95% CI 0.01-0.05), p=0.037 favoring FMT
• Safety: all AEs transient and non-serious; no significant change in LEDD
Clinical Question
In adults with Parkinson's disease on oral levodopa, does a single donor-derived fecal microbiota transplantation via colonoscopy improve motor symptoms (MDS-UPDRS III OFF at 12 months) and non-motor symptoms compared with autologous-FMT placebo?
Bottom Line
A single donor-derived FMT did not improve the primary motor outcome (MDS-UPDRS III OFF at 12 months) in PD, but produced significant improvements in several non-motor domains (total NMS score, GI dysfunction, quality of life, UPDRS I/II) and a transient early benefit on MDS-UPDRS III ON, with a favorable safety profile.
Major Points
- First rigorously placebo-controlled RCT using autologous-FMT as the comparator, minimizing procedural placebo effects
- Primary endpoint (MDS-UPDRS III OFF at 12 months) was NOT met — DiD 1.5 (95% CI -1.5 to 4.4), adjusted p=1.00
- Significant early motor benefit in ON state at 1 month (DiD -3.5, p<0.001) that was not sustained beyond 3 months
- Consistent 12-month benefit on non-motor symptoms: MDS-NMS total, GIDS-PD, EQ-5D quality of life, and MDS-UPDRS I and II all favored donor-derived FMT
- Signal for pain-domain improvement at 1, 3, and 12 months in the FMT arm
- Safety was favorable: all procedure-related AEs were transient and non-serious; no change in levodopa equivalent daily dose
- Results suggest more intensive or repeated FMT dosing, or earlier-stage patients, may be needed to achieve durable motor benefit
Study Design
- Study Type
- Randomized Controlled Trial
- Randomization
- Yes
- Blinding
- Double-blind (patients and clinicians blinded; only HBI manufacturing personnel unblinded)
- Sample Size
- 59
- Follow-up
- 12 months (assessments at baseline, 1, 3, 6, and 12 months)
- Centers
- 1
- Countries
- Poland
Primary Outcome
Definition: Change in MDS-UPDRS III (Motor Examination) in the OFF state at 12 months compared to baseline
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Baseline 22.5 (SE 2.1); 12-mo change +1.5 (95% CI -0.6 to 3.7) | Baseline 21.5 (SE 2.0); 12-mo change +3.0 (95% CI 1.0 to 5.0) | N/A (mean difference reported) (DiD -1.5 to 4.4) | 1.00 (adjusted; unadjusted 0.326) |
Limitations & Criticisms
- Small sample size (N=59) limits power to detect modest motor effects and to characterize subgroups
- Single-center study conducted in Poland — limits generalizability
- Only a SINGLE FMT administration was used; sustained effects on motor symptoms may require repeated dosing
- Predominantly moderate-to-advanced PD (median symptom duration 5-6 years; LEDD ~750-800 mg); Bruggeman et al showed larger effects in early-stage PD (disease duration 4.2 vs 5 yr)
- Multiple secondary outcomes and time points tested — despite Bonferroni adjustment, risk of type I error remains for the many nominally significant non-motor findings
- Detailed body-first vs brain-first PD phenotyping not performed; microbiota composition changes not fully characterized in this report
- BMI differed at baseline (bold significant p=0.015 favoring higher BMI in Mbiotix group), potentially confounding despite covariate adjustment
- Colonoscopy-based administration is invasive; less invasive delivery (e.g., capsules) not tested
- A conflict of interest exists: J. Biliński is a shareholder of Human Biome Institute, the manufacturer of Mbiotix HBI
- Auto-FMT is a novel placebo but its microbiological neutrality is not fully validated
Citation
Ann Neurol 2026;100:10-21