Mediterranean-ketogenic vs. medium-chain triglyceride supplemented Mediterranean diet: Effects on the gut-brain-immune axis in Parkinson’s disease

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.