Objective: To investigate the effect of exogenous oral ketone esters on gut microbiota in people with PD.

Background: Mitochondrial dysfunction in the substantia nigra and subsequent production of pathological reactive oxygen species (ROS) is believed to exacerbate PD pathology and progression. Preliminary human data suggest high-fat, low-carbohydrate ketogenic diet positively impact PD symptoms through improved metabolic efficiency and reduced neuroinflammation [Figure 1]. Exogenous oral ketone esters (KE) provide rapid, consistent, and sustained elevation of circulating ketones following ingestion. These KE may also have an effect on the gut microbiota with the potential to increase alpha diversity (species richness), ameliorate dysbiosis, and dampen neuroinflammation as has been shown in animal studies.

Method: In this prospective, single-arm, single-center pilot study, 10 people with PD consumed an exogenous ketone ester drink four times per day for four weeks. In addition to neurological, functional, and cognitive assessments prior to and after supplementation (published previously), fecal samples were collected pre- and post- ketone supplementation. DNA from each stool sample was extracted and microbiota was analyzed using 16S rDNA amplified and sequenced, and analyzed using QIIME2 and RStudio.

Results: Stool samples from 8 patients were analyzed. There was insignificant intra- and interindividual variation in microbiota pre- and post-ketone intervention at the individual phylum level although a slight increase in Firmicutes:Bacteroidetes ratio was observed (1.43 vs. 1.72). No significant differences were observed in alpha diversity (Shannon and Simpson) between time points. While we observed microbiota variation over time at the family level, no ketone associated differences were observed at either phylum or family level.

Conclusion: These results may indicate that exogenous ketone supplements cause minimal changes in microbiota, at least in our short-term intervention. Further longitudinal studies are needed to explore changes in blood ketone concentrations, microbiota, and long-term tolerability.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-an-exogenous-ketone-supplement-on-gut-microbiota-in-parkinsons-disease-a-pilot-study/