(P19-040-25) Dietary Patterns and Gut Microbiome Dynamics: A Meta-Analysis of Mediterranean and Ketogenic Diets

Objectives: To conduct a comprehensive and statistically robust evaluation of the effects of Mediterranean and Ketogenic diets on gut microbiome profiles through meta-analysis.

Methods: Publicly available sequencing data from clinical longitudinal and cross-sectional studies using metabarcoding strategies were collected for meta-analysis. Seven studies on Mediterranean diet (MD) interventions (5-weeks to 6-months) or adherence to MD were included, analyzing 111 paired samples (before/after intervention) and 124 subjects (53 low- vs. 71 high-adherence). Additionally, seven studies on ketogenic diet (KD) interventions (4-weeks to 1-year) were analyzed, including 156 paired samples.

Results: Both the MD and KD induced considerable shifts in the gut microbiome. While both diets increased microbial diversity, the effect was more pronounced with MD (p=0.025) compared to KD (p=0.130). However, KD elicited more dynamic compositional changes overall. Specifically, several important short-chain fatty acids (SCFAs)-producing bacteria including Bifidobacterium, Agathobacter, and multiple genera within the family Ruminococcaceae were significantly reduced in KD (Wilcoxon Signed-Rank test, p< 0.05). Concurrently, sulfate-reducing bacteria that generate hydrogen sulfide (H₂S), along with genera in the Proteobacteria phylum, expanded under KD. Reflecting these compositional shifts, the microbiome’s functional capacity showed an enrichment in lipid-related pathways, including the synthesis and degradation of ketone bodies as well as fatty acid degradation. In contrast, MD was associated with an increase in bacteria known to utilize pectin or complex carbohydrates and produce SCFAs, including bacterial genera Monoglobus, Butyricimonas, and multiple genera within Lachnospiraceae family. Although MD did not result in significant changes to overall metabolic pathways, functional pathways related to bacterial invasion of epithelial cells were notably diminished.

Conclusions: The MD and KD patterns induce distinct shifts in the gut microbiome composition, with MD generally showing more favorable changes. This underscores the importance of selecting dietary interventions and durations with careful consideration of their long-term effects on gut microbiome and overall intestinal health.

Funding Sources: Florida State University