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Mbiotix-PD

Safety and Efficacy of Fecal Microbiota Transplantation in Alleviating Symptoms of Parkinson's Disease: A Randomized, Placebo-Controlled, Double-Blinded Study

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Year of Publication: 2026

Authors: Figura M, Milanowski Ł, Nowak JM, et al.

Journal: Annals of Neurology

Citation: Ann Neurol 2026;100(1):10–21. DOI: 10.1002/ana.78153

Link: https://doi.org/10.1002/ana.78153

Clinical Question

Does a single donor-derived fecal microbiota transplant, delivered by colonoscopy, improve motor (MDS-UPDRS III “OFF”) and non-motor symptoms of Parkinson disease over 12 months compared with autologous-stool placebo FMT?

Bottom Line

A single colonoscopy-delivered donor FMT did NOT improve the primary motor endpoint (MDS-UPDRS III “OFF”) at 12 months in PD, but produced significant, mostly modest improvements in several non-motor domains (total MDS-NMS, pain, cognition subscale, sexual dysfunction, GI dysfunction) and in EQ-5D quality of life at 12 months. The procedure was safe with only transient GI adverse events.

Major Points

  • Design: prospective, parallel-group, randomized 1:1, double-blind, placebo (auto-FMT)-controlled, single-center trial at Medical University of Warsaw / Mazovian Brodnowski Hospital, Poland; enrollment Jan 2022–Aug 2023; 12-month follow-up.
  • Population: 59 patients with MDS-criteria PD on oral levodopa, aged 40–75 y (median 65 y Mbiotix / 63 y placebo); 30 female (50.8%), 29 male (49.2%); median symptom duration 5–6 y; baseline LEDD ~796 (Mbiotix) vs ~742 (placebo) mg/day; BMI higher in Mbiotix (27.2 vs 25.8 kg/m², p=0.015).
  • Intervention: single 60 g donor stool suspended in 200 mL saline with 10% glycerol, injected into cecum via colonoscopy after 5-day rifaximin + bowel prep; comparator: identically prepared autologous (patient's own) stool.
  • Primary outcome (MDS-UPDRS III “OFF” at 12 mo): DiD +1.50 (95% CI −4.28 to 7.28, p=1.00 Bonferroni-adjusted) — no difference; both arms slightly worsened (∆ +3.0 Mbiotix vs +1.5 placebo).
  • MDS-UPDRS III “ON” at 1 mo showed early significant benefit (DiD −3.5, 95% CI −5.2 to −1.8, p<0.001) that was not sustained.
  • Non-motor: MDS-NMS total at 12 mo DiD −20.3 (95% CI −35.2 to −5.4, adj p=0.030); pain subscale reductions at 1 mo (−3.9), 3 mo (−4.9), and 12 mo (−3.6), all p<0.001; cognition subscale at 3 mo DiD −5.5 (p<0.001); sexual dysfunction at 6 mo DiD −1.8 (p<0.001).
  • GI: GIDS-PD at 12 mo DiD −4.4 (95% CI −6.9 to −1.8, p=0.003) favoring FMT; mCAS unchanged.
  • Quality of life: EQ-5D at 12 mo DiD +0.03 (95% CI 0.01–0.05, p=0.037) favoring FMT (placebo group declined); PDQ-39 no significant difference.
  • MoCA: within-group improvement in Mbiotix (∆ +0.90, p=0.049) but between-group difference NS (DiD 0.6, 95% CI −0.01 to 1.3, p=0.10).
  • LEDD unchanged in both arms (12-mo DiD ~−4, p=1.000).
  • Safety: only transient GI adverse events (abdominal pain, diarrhea, constipation, heartburn, nausea, painful defecation, fever); no serious procedure-related events; 36/59 (61%) chose general anesthesia for colonoscopy.

Design

Study Type: Randomized, parallel-group, double-blind, placebo (autologous-FMT)-controlled trial

Randomization: 1

Blinding: Double-blind (patients and clinicians blinded to allocation; only the head of the HBI Manufacturing Laboratory was unblinded to prepare/label samples). Sealed-Envelope software; 1:1; stratified by PD stage (early vs advanced).

Enrollment Period: January 2022 – August 2023

Follow-up Duration: 12 months (assessments at baseline, 1, 3, 6, and 12 mo; MoCA at baseline and 12 mo)

Centers: 1

Countries: Poland

Sample Size: 59

Power Calculation: Powered on primary DiD estimator at 12 mo (2-sample t-test approximation, Cohen's d = 0.8, 80% power, α=0.05): 21/arm minimum, inflated to 26/arm (52 total) to account for 15–20% attrition.

Analysis: Intention-to-treat using a robust linear mixed-effects model with treatment, time, treatment×time, age, sex, BMI as fixed effects and group-level random effects; robust estimation; predictive-mean-matching imputation for missing data (assumed MNAR); DiD estimator; Bonferroni adjustment across 4 timepoints (adjusted α=0.0125); effect sizes as Cohen's d.

Inclusion Criteria

  • Diagnosis of Parkinson disease per MDS clinical diagnostic criteria
  • Ongoing oral levodopa treatment
  • Age 40–75 years
  • Written informed consent

Exclusion Criteria

  • Contraindications for colonoscopy (history of gastrointestinal perforation or obstruction)
  • Post-radiotherapy status of the abdominal or rectal area
  • Severe heart, kidney, or liver failure
  • Coagulation disorders
  • Congenital or acquired immune deficiencies
  • Current viral, bacterial, or fungal infection
  • Abdominal aortic aneurysm requiring surgery
  • Pregnancy or lactation
  • Treatment with dopaminergic infusion therapies
  • Deep brain stimulation
  • Colorectal polyps at colonoscopy (except lesions <5 mm classified as NBI International Colorectal Endoscopic type I) or other potentially neoplastic changes
  • Strong food allergy with history of anaphylaxis
  • Stool positive for MDR/pathogenic bacteria (MRSA, KPC, MBL- or ESBL-producing organisms, VRE, Salmonella, Shigella, Yersinia)

Baseline Characteristics

CharacteristicMbiotix (n=28)Placebo / auto-FMT (n=31)
Sex - Female n (%)13 (46%)17 (55%)
Sex - Male n (%)15 (54%)14 (45%)
Median age, y (IQR)65.0 (58.0–69.3)63.0 (56.5–67.0)
Median BMI, kg/m² (IQR)27.20 (25.78–30.58)25.80 (24.20–27.35)
Median age at diagnosis, y (IQR)57.5 (48.8–66.0)56.0 (49.5–61.0)
Median symptom duration, y (IQR)5.0 (2.8–7.0)6.0 (2.0–7.5)
Smoking, n (%)3 (11%)4 (13%)
Coffee consumption, n (%)23 (82%)26 (84%)
Baseline MDS-UPDRS III OFF (EMM, 95% CI)21.5 (17.6–25.4)22.5 (18.4–26.6)
Baseline MDS-UPDRS III ON (EMM, 95% CI)12.6 (10.2–15.0)12.8 (10.4–15.2)
Baseline MoCA (EMM, SE)25.9 (0.9)24.8 (0.5)
Baseline LEDD, mg (EMM, 95% CI)796 (625–967)742 (563–921)
Baseline MDS-NMS total (EMM, 95% CI)93.8 (73.6–114.0)79.5 (58.3–100.7)
Baseline GIDS-PD (EMM, 95% CI)14.8 (11.4–18.3)14.6 (11.0–18.2)
Baseline PDQ-39 (EMM, 95% CI)32.5 (25.2–39.8)29.7 (22.0–37.4)
Baseline EQ-5D (EMM, 95% CI)0.91 (0.89–0.93)0.91 (0.89–0.93)

Arms

FieldMbiotix (donor FMT)Control
InterventionSingle donor-derived FMT: 60 g SuperDonor stool in 200 mL 0.9% NaCl with 10% glycerol (Mbiotix, Human Biome Institute), stored at −80°C and thawed at room temperature, delivered into cecum via colonoscopy after 5-day rifaximin 400 mg PO tid + bowel prep with macrogol 4000.Single autologous FMT: identically prepared 60 g suspension of the patient's own stool (collected before antibiotic pretreatment) in 200 mL 0.9% NaCl with 10% glycerol, delivered into cecum via colonoscopy after 5-day rifaximin 400 mg PO tid + bowel prep.
N2831

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Change in MDS-UPDRS Part III (motor examination) “OFF” state score from baseline to 12 months, Mbiotix vs placebo (auto-FMT).Primary12-mo EMM 24.0 (95% CI 19.9–28.1); change from baseline +1.5 (95% CI −0.6 to 3.7)12-mo EMM 24.5 (95% CI 20.6–28.4); change from baseline +3.0 (95% CI 1.0 to 5.0)1.00 (Bonferroni-adjusted across 4 timepoints)
MDS-UPDRS III “ON” at 1 mo (DiD)Secondary∆ +1.5 [+0.3, +2.7]∆ −2.0 [−3.2, −0.8]<0.001
MDS-UPDRS III “ON” at 12 mo (DiD)Secondary∆ +1.6∆ +0.40.168
MoCA at 12 mo (DiD)Secondary∆ +0.30∆ +0.900.10 (adjusted)
MDS-UPDRS I at 12 mo (DiD)Secondary∆ +0.6∆ −0.10.028
MDS-UPDRS II at 12 mo (DiD)Secondary∆ 0.0∆ −1.0<0.001
MDS-UPDRS IV at 12 mo (DiD)Secondary∆ −0.5∆ −0.31.000
MDS-NMS total at 12 mo (DiD)Secondary∆ −1.2∆ −21.50.030
MDS-NMS cognition subscale at 3 mo (DiD)Secondary∆ −0.1∆ −5.5<0.001
MDS-NMS sexual dysfunction at 6 mo (DiD)Secondary∆ +0.7∆ −1.1<0.001
MDS-NMS pain at 1 mo (DiD)Secondary∆ −0.2∆ −4.1<0.001
MDS-NMS pain at 3 mo (DiD)Secondary∆ +1.8∆ −3.2<0.001
MDS-NMS pain at 12 mo (DiD)Secondary∆ 0.0∆ −3.6<0.001
MDS-NMS 'other' (fatigue/weight/sweating/olfaction) at 12 mo (DiD)Secondary∆ +2.76∆ −2.9<0.001
GIDS-PD total at 12 mo (DiD)Secondary∆ +1.2∆ −3.20.003
mCAS at 12 mo (DiD)Secondary∆ −0.2∆ −0.80.768
PDQ-39 at 12 mo (DiD)Secondary∆ +3.6∆ −0.80.296
EQ-5D at 12 mo (DiD)Secondary∆ −0.03∆ 0.000.037
LEDD (mg) at 12 mo (DiD)Secondary∆ +18∆ +671.000
Any procedure-related adverse eventSafetysame profiletransient GI symptoms only (abdominal pain, diarrhea, constipation, heartburn, epigastric fullness, nausea, painful defecation, fever)
Serious adverse events attributed to procedureSafety0/310/28
Colonoscopy performed under general anesthesiaSafety16/31 (52%)19/28 (68%)
DiscontinuationsSafety—1 randomized patient excluded intra-procedure for pneumatosis cystoides intestinalis (before FMT); 1 patient lost to follow-up after visit 1

Subgroup Analysis

Randomization was stratified by PD stage (early vs advanced), but no formal subgroup analyses of primary/secondary outcomes by stage, sex, or symptom duration are reported. Authors discuss that Bruggemann et al. (GUT-PARFECT) recruited only early-stage patients (shorter disease duration, lower LEDD) and reported motor benefit, suggesting a possible early-PD-specific effect that this mixed cohort could not detect.

Criticisms

  • Small sample (N=59) with wide confidence intervals — the primary MDS-UPDRS III OFF DiD 95% CI (−4.28 to 7.28) spans clinically important benefit and harm, so a modest true effect cannot be excluded (type II error risk acknowledged by authors).
  • Single-center trial in Warsaw, Poland — limited generalizability.
  • Mixed early and advanced PD population; higher baseline LEDD (~750–800 mg) than GUT-PARFECT's early-PD cohort, which is where prior FMT motor benefit was seen — the negative primary result may reflect stage selection.
  • Single FMT dose — authors themselves hypothesize that repeated dosing may be required to sustain the early MDS-UPDRS III 'ON' benefit and to produce OFF-state effects.
  • Multiple secondary endpoints with Bonferroni adjustment only across 4 timepoints (not across scales) — the many positive non-motor subscale findings should be considered exploratory / hypothesis-generating.
  • No detailed microbiome baseline typing or body-first vs brain-first phenotyping; abnormal baseline microbiota was not an inclusion criterion, unlike Scheperjans's cohort.
  • Baseline BMI imbalance (higher in Mbiotix, p=0.015) despite randomization — handled via covariate adjustment in the mixed model but residual confounding possible.
  • Blinding integrity of autologous vs donor FMT not formally assessed (both products identically packaged and stored, but no post-trial guess questionnaire reported).
  • Sponsor conflict of interest: last-author J. Biliński is a shareholder of Human Biome Institute, the manufacturer of Mbiotix.

Funding

Biocodex Microbiota Foundation National Grant 2021; Medical University of Warsaw grants 09/M/MBS/N/21, 1/Z/MG/24, NZP/1/Z/MG/N/23, and M/MG/77/22. Funders had no role in design or interpretation. Mbiotix product supplied by Human Biome Institute (Warsaw, Poland).

Based on: Mbiotix-PD (Annals of Neurology, 2026)

Authors: Figura M, Milanowski Ł, Nowak JM, et al.

Citation: Ann Neurol 2026;100(1):10–21. DOI: 10.1002/ana.78153

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