A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease Original paper

What was studied?

This study, titled “A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease,” aimed to evaluate whether a short-term, fiber-rich prebiotic diet could modulate the gut microbiome and its metabolites in patients with Parkinson’s Disease (PD), with a particular emphasis on short-chain fatty acids (SCFAs) and microbial metabolic signatures of potential neuroprotective relevance. The intervention consisted of a 4-week diet high in dietary fiber and daily intake of the prebiotic Lactulose. Researchers conducted comprehensive profiling, including gut metagenomics, faecal and urinary metabolomics, and clinical assessments (motor and gastrointestinal symptoms), to determine the effects of this dietary intervention on microbial composition, SCFA production, gut-brain-relevant metabolites, and clinical parameters.

Who was studied?

The study population consisted of 11 couples, each comprising a patient with idiopathic Parkinson’s Disease (mild to moderately advanced, Hoehn and Yahr stages 1–2) and their healthy spouse as a control (CO). Ten couples completed the intervention, resulting in 10 PD patients and 10 matched controls. All participants were aged ≤75 years, followed omnivorous diets, and were screened for exclusion criteria such as recent antibiotic use, gastrointestinal diseases, or veganism. The inclusion of spousal controls was designed to minimize dietary and environmental variability, given the pronounced “household effect” on microbiome composition. PD subjects started Lactulose for constipation management at the time of study entry, while controls received a prebiotic dose, ensuring matched intervention exposure.

Most important findings

The most significant findings centered on microbiome composition, metabolite profiles, and clinical outcomes. At baseline, PD patients displayed reduced faecal SCFA concentrations and characteristic gut bacterial dysbiosis, notably depletion of SCFA-producing taxa such as Blautia, Dorea, and Erysipelatoclostridium. Following the prebiotic intervention, both PD and control groups exhibited increased faecal SCFA levels, with a particularly notable rise in propionate among PD patients. This increase in SCFAs correlated inversely with disease severity and gastrointestinal symptom scores in PD, indicating possible clinical benefits.

Taxonomically, the diet induced a robust enrichment of multiple Bifidobacterium species in both groups, likely attributable to Lactulose, but failed to fully restore the PD-associated dysbiotic signature—key taxa remained depleted in PD after intervention. Importantly, urinary and faecal metabolomics demonstrated normalization of several PD-associated metabolite aberrations after the intervention, including reductions in potentially neurotoxic compounds (e.g., p-cresol sulfate, quinolinic acid) and increases in neuroprotective metabolites (e.g., myo-inositol, glutathione). Functional metagenomics revealed increased microbial genes related to fatty acid metabolism, glutathione synthesis, and other neuroprotective pathways in PD post-intervention. However, certain PD-specific microbial functional signatures, such as enhanced drug resistance and tryptophan degradation, persisted.

Key implications

This pilot study provides compelling evidence that a short-term, prebiotic-rich dietary intervention can beneficially modulate the gut microbiome and metabolite output in PD patients, particularly by enhancing SCFA production and shifting metabolic pathways toward neuroprotection. Importantly, these changes were accompanied by improvements in gastrointestinal symptoms and trends toward reduced motor severity. The marked enrichment of Bifidobacteria underscores the need to consider Lactulose use in microbiome studies of PD, as it may confound disease-specific microbial signatures. However, the persistence of core dysbiotic taxa in PD suggests that longer or more targeted interventions may be needed to fully normalize the gut ecosystem. For clinicians, these findings highlight the therapeutic promise of microbiota-directed dietary strategies in PD—especially for patients with fiber-deficient diets—but also the necessity for personalized, strain-specific approaches and careful consideration of potential interactions with standard PD treatments. Larger, longer-term, and placebo-controlled studies are required to validate these results and optimize intervention protocols.

Citation

Bedarf JR, Romano S, Heinzmann SS, Duncan A, Traka MH, Ng D, Segovia-Lizano D, Simon MC, Narbad A, Wüllner U, Hildebrand F. A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease. npj Parkinson’s Disease. 2025;11:66. doi:10.1038/s41531-025-00885-5