Despite extensive research, current treatment of Parkinson’s Disease (PD) remains symptomatic and disease modifying approaches are urgently required. A promising approach is to target the gut-brain-axis by modifying the intestinal microbiota and the herein produced metabolites.

We decided to test this approach by modifying key metabolites of bacterial intestinal fermentation: short chain fatty acids (SCFA), known to be decreased in PD patients. A prospective, controlled pilot study was conducted in 11 couples, with one PD patient and healthy spouse as control (CO) each. Participants followed a 4-week diet rich in dietary fibre in addition to the intake of a prebiotic sirup (Lactulose). Metagenomes and metabolites of the gut microbiota, urinary metabolites and clinical characteristics were assessed.

The short-term dietary intervention significantly augmented gastrointestinal SCFA production, likely associated with increased Bifidobacteria spp. PD associated gastrointestinal symptoms improved with increasing SCFA levels. The pre-existing bacterial dysbiosis associated with PD, such as depletion of genera Blautia, Dorea, and Erysipelatoclostridium in PD, persisted within the study period. Some pathobionts, i.e. Klebsiella, were reduced after the intervention. Bacterial metabolite composition (both faecal and urine metabolomes) shifted towards the composition of the healthy control in PD after the intervention. Among these brain-relevant gut metabolic functions improved in PD patients, such as S-Adenosyl methionine (SAM), 3,4-Dihydroxyphenylacetic acid (DOPAC), Glutathione (GSH), Tryptophan and inositol related changes, involved in neuroprotective and antioxidant pathways.

Despite the small cohort size and short-term study period a minor dietary intervention was sufficient to improve gastrointestinal symptoms in PD and altered metabolic parameters in a presumed neuroprotective manner, warranting further investigation in larger cohorts.

The authors have declared no competing interest.

DRKS00034528

This study was funded by the Hilde-Ulrichs-Foundation for Parkinson's research. This research was also supported by the BBSRC Institute Strategic Programme (ISP) Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/F/000PR13631, the BBSRC Core Capability Grant BB/CCG2260/1 and its constituent project BBS/E/QU/23NB0006, the ISP Decoding Biodiversity BBX011089/1, projects BBS/E/ER/230002A and BBS/E/ER/230002B, and Cellular Genomics Cellular Genomics BBX011070/1, project BBS/E/ER/230001A. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. JRB was supported by a local grant (FEMHabil) at the medical faculty of the University Hospital Bonn. FH was supported by European Research Council H2020 StG (erc-stg-948219, EPYC). We thank Lia Mareen Taube for her support during the study performance.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics committee of the University of Bonn, Germany, gave ethical approval for this work (internal ethics vote 145/17).

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The metagenomic sequencing data generated and/ analysed during the current study is available in the European Nucleotide Archive, ENA repository, PRJEB57228. Further data types are available upon request from the corresponding authors.