, results of a new, randomized placebo-controlled trial show.
However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.
“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded.
The study was published online in JAMA Neurology.
Gut Dysfunction: An Early Symptom
Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression.
Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease.
Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.
In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.
All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment.
Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.
The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.
Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.
Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group.
Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group.
The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms.
In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible.
The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect.
“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded.