Placebo-Controlled Trial Finds Repeated Fecal Transplants Ease Motor Symptoms in Early Parkinson's

A phase 2 randomized trial reports that repeated donor stool transplants outperformed transplants of patients' own stool on motor and constipation scores in drug-naive Parkinson's disease, the first controlled efficacy data since earlier reporting on gut changes that precede diagnosis.

A randomized, double-blind, placebo-controlled phase 2 trial has found that repeated donor fecal microbiota transplants eased motor symptoms and constipation in people with early, drug-naive Parkinson's disease more than transplants of their own stool did. In the 72-patient trial, published March 13, 2026 in Signal Transduction and Targeted Therapy, patients who received donor material showed a mean improvement of 3.8 points on the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRS-III) at 35 weeks, versus a 0.1-point worsening in the group that received their own banked stool (p = 0.0001); constipation severity fell by 6.5 points in the donor group versus 0.7 points in the control group (p < 0.0001).

The trial is the first sham-controlled efficacy test of repeated fecal transplantation in people not yet taking Parkinson's medication, a population researchers say is cleaner for isolating a gut-based effect from drug effects. It follows a smaller 2024 trial, GUT-PARFECT, which gave a single donor infusion to patients already on standard Parkinson's drugs and reported a modest, long-lasting motor benefit; the new study instead delivered repeated seven-day infusion courses, of donor or autologous material, across successive four-week cycles, with the patient's own stool serving as the blinded comparator rather than an inert placebo. Sixty-six of the 72 enrolled patients completed the full 35 weeks of follow-up.

Alongside the clinical scores, the researchers reported that donor recipients' gut bacteria shifted to more closely resemble their donors', with a marked drop in Escherichia-Shigella that correlated with lower colonic alpha-synuclein aggregation (r = 0.3775, p = 0.0277). Fecal dopamine and its metabolite DOPAC rose, and markers of gut lining integrity, including E-cadherin, increased in donor recipients. All adverse events in the trial were described by the authors as mild and self-limited, with no serious treatment-related events reported.

The trial's authors and outside readers of the gut-Parkinson's literature caution that one 72-person study, run at a single point in the disease course and followed for 35 weeks, is not the same as proof the treatment changes the long-term course of Parkinson's. Because the control arm received the patients' own transplanted stool rather than a saline sham, it is also not a fully inert comparison, a design choice made for blinding that leaves open how much of the control group's smaller changes reflect the procedure itself. Larger, independent, multi-site trials with longer follow-up would be needed before the approach could be evaluated for clinical use.