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COPENHAGEN — Giving patients with Parkinson’s disease and constipation a probiotic for 3 months improved not only their gut microbiome but also nonmotor symptoms such as sleep, fatigue, and constipation, results of a new randomized trial show.

Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, procyclidine for anxiety PhD, Department of Neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom.

Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2023.

“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Leta told attendees of the congress.

A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including pro-inflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”

However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited…to the treatment of constipation,” she explained.

The team therefore conducted a multicenter, randomized, double-blind, placebo controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.

The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.

A total of 74 patients were randomly assigned to the two study arms. The two groups were well-matched for sociodemographic, Parkinson’s disease, and constipation-related characteristics, Leta reported, and only three patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events,” she added.

Increase in Healthy Bacteria

The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.

The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Leta said.

This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”

The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the post-intervention assessment (P < .027).

There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the post-intervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).

This, Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”

No such significant improvements were observed in the placebo arm.

Probiotics ‘Hot Topic’ Among Patients

Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen, Goettingen, Germany, told Medscape Medical News that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”

Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.

“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”

The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”

This, she argued, could have resulted in better absorption of levodopa.

A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”

Beyond Constipation?

Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”

Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,'” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.

Veronica Bruno, MD, MPH, assistant professor in the Department of Clinical Neurosciences at the University of Calgary, Calgary, Alberta, Canada, commented in a release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.

The current study “stands out as a significant contribution to this area of study,” she said.

“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”

Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”

The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.

International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2023. Abstract 84. Presented August 29, 2023.

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