Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairmentOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
Researchers examined whether the gut microbiome differs between older adults with mild cognitive impairment (MCI) and cognitively normal peers. They also tested whether a modified Mediterranean-ketogenic diet (MMKD) shifts the microbiome and short-chain fatty acids (SCFAs) alongside cerebrospinal fluid (CSF) Alzheimer's disease biomarkers.
How was it studied?
A randomized, double-blind, cross-over pilot trial enrolled 17 adults (mean age 64.6), 11 with MCI and 6 cognitively normal. Each completed six weeks of MMKD and six weeks of an American Heart Association Diet (AHAD), separated by a six-week washout, with stool, fecal SCFAs, and CSF amyloid beta and tau measured before and after each diet.
What did they find?
At baseline, MCI subjects showed higher Proteobacteria and Enterobacteriaceae and lower Bacteroidetes, and Proteobacteria correlated positively with the Aβ-42:Aβ-40 ratio while fecal propionate and butyrate correlated negatively with Aβ-42. MMKD increased Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae, and Erysipelotrichaceae while reducing Bifidobacterium and Lachnobacterium, and it raised fecal propionate and butyrate while slightly lowering lactate and acetate; AHAD showed the opposite SCFA pattern, raising acetate and propionate but lowering butyrate.
Why it matters
The findings suggest specific gut microbial signatures track mild cognitive impairment and that MMKD can shift gut microbes and metabolites in ways linked to more favorable CSF Alzheimer's biomarkers. The pilot's small size (17 subjects) means these signatures need validation in larger cohorts.