In a 12‑week randomized, double‑blind, placebo‑controlled trial of a nine‑strain probiotic in 61 people with PD and clinically significant anxiety, the probiotic did not reduce anxiety versus placebo, produced no detectable changes in gut microbiota composition or systemic inflammatory markers, but…

The negative primary outcome limits immediate therapeutic relevance, but the modest cognitive signal and gut–brain axis approach justify larger, mechanistically focused trials to assess microbiome‑based strategies for cognitive symptoms in PD.

Anxiety is a prevalent non-motor symptom of Parkinson's disease (PD), yet treatment options remain limited. This randomized, double-blind, placebo-controlled trial evaluated the effects of a 12-week probiotic supplement containing nine bacterial strains (Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, and Lactococcus lactis W19 and W58) on anxiety symptoms in 61 individuals with PD and clinically significant anxiety. Both the probiotic (n = 30) and placebo (n = 31) groups showed significant within-group improvements on the Parkinson Anxiety Scale, with no significant between-group differences. The probiotic group showed a statistically significant improvement on the Montreal Cognitive Assessment compared with placebo (adjusted mean difference of 1.1 points; 95% confidence interval: 0.04-2.1; p = 0.043). No treatment effects were seen on other secondary outcomes, including depression, constipation, or motor symptoms. No significant between-group differences in gut microbiota composition or systemic inflammatory markers were observed. While the multi-strain probiotic did not reduce anxiety more than placebo, its potential cognitive effects warrant further investigation in larger trials. This trial was registered on ClinicalTrials.gov (NCT03968133) on May 28, 2019.