Mediterranean-ketogenic vs. medium-chain triglyceride supplemented Mediterranean diet: Effects on the gut-brain-immune axis in Parkinson’s disease
Abstract
Ketogenic diets have been proposed as potential neuroprotective interventions for Parkinson’s disease (PD), but concerns remain regarding their effects on the gut microbiome and gut-brain-immune axis. We conducted a randomized crossover trial comparing 8-week Mediterranean-ketogenic (MeDi-KD) versus medium-chain triglyceride-supplemented Mediterranean (MeDi-MCT) diets, separated by an 8-week washout (NCT05469997). Primary outcomes included changes in gut microbiome taxonomic and functional profiles, fecal short-chain fatty acid (SCFA) production, and biomarkers of intestinal permeability and inflammation. Neither intervention significantly altered microbiome diversity or functional gene abundance, established features of PD-associated dysbiosis, nor fecal or plasma biomarkers of intestinal permeability (zonulin) or inflammation (calprotectin). The MeDi-KD modestly reduced total fecal SCFAs, while both interventions increased the relative abundance of Roseburia hominis, and the MeDi-MCT was associated with decreases in plasma IL-1β and IL-8. No severe adverse events were reported, supporting further investigation of MeDi-KD strategies in larger, longer-duration PD trials.
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BibTeX
@article{tosefsky2026mediterraneanketogenic,
title = {{Mediterranean-ketogenic vs. medium-chain triglyceride supplemented Mediterranean diet: Effects on the gut-brain-immune axis in Parkinson’s disease}},
author = {Kira Tosefsky and Samantha L. Schaffner and Joyce S.T. Lam and Yolanda N. Wang and Shayan Keymanesh and Annie J. Kuan and Avril Metcalfe-Roach and Mihai S. Cirstea and Matthew A. Sacheli and Tessa F. Morelli and Matthew Yap and Olivia Brigden and Madison Gill and Tamara R. Cohen and Sophie Stukas and B. Brett Finlay and Silke Appel-Cresswell},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117981},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03364-X},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mediterranean-ketogenic vs. medium-chain triglyceride supplemented Mediterranean diet: Effects on the gut-brain-immune axis in Parkinson’s disease
AU - Kira Tosefsky
AU - Samantha L. Schaffner
AU - Joyce S.T. Lam
AU - Yolanda N. Wang
AU - Shayan Keymanesh
AU - Annie J. Kuan
AU - Avril Metcalfe-Roach
AU - Mihai S. Cirstea
AU - Matthew A. Sacheli
AU - Tessa F. Morelli
AU - Matthew Yap
AU - Olivia Brigden
AU - Madison Gill
AU - Tamara R. Cohen
AU - Sophie Stukas
AU - B. Brett Finlay
AU - Silke Appel-Cresswell
PY - 2026
DA - 2026/10/28
JO - iScience
DO - 10.1016/j.isci.2026.117981
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03364-X
AB - Ketogenic diets have been proposed as potential neuroprotective interventions for Parkinson’s disease (PD), but concerns remain regarding their effects on the gut microbiome and gut-brain-immune axis. We conducted a randomized crossover trial comparing 8-week Mediterranean-ketogenic (MeDi-KD) versus medium-chain triglyceride-supplemented Mediterranean (MeDi-MCT) diets, separated by an 8-week washout (NCT05469997). Primary outcomes included changes in gut microbiome taxonomic and functional profiles, fecal short-chain fatty acid (SCFA) production, and biomarkers of intestinal permeability and inflammation. Neither intervention significantly altered microbiome diversity or functional gene abundance, established features of PD-associated dysbiosis, nor fecal or plasma biomarkers of intestinal permeability (zonulin) or inflammation (calprotectin). The MeDi-KD modestly reduced total fecal SCFAs, while both interventions increased the relative abundance of Roseburia hominis, and the MeDi-MCT was associated with decreases in plasma IL-1β and IL-8. No severe adverse events were reported, supporting further investigation of MeDi-KD strategies in larger, longer-duration PD trials.
SN - 2589-0042
ER -