(P19-001-25) An Eight-Week Well-Formulated Ketogenic Diet Alters the Functional Composition of the Gut Microbiome

Objectives: A ketogenic diet (KD) shifts glucose metabolism to fat metabolism and promotes ketones bodies as the body’s primary source of fuel. Our data, as well as findings from other KD studies, suggest that a KD alters the gut microbiome. The objective of this study was to investigate changes in the function of the gut microbial composition after an 8-week nutrient dense, well-formulated KD (WFKD) intervention.

Methods: Twenty generally healthy, non-smoking participants aged 30-55 years were allocated to a single-arm, 8-week WFKD intervention. Participants provided stool samples (OMR-200, DNAGenotek, Canada) at baseline and 8 weeks. We extracted genomic DNA (gDNA) from 250 µL of stool using QIAamp Power Fecal Pro DNA Kits (QIAGEN, Germany) on the QIAcube Connect system and diluted to 5 ng/µL for library preparation. We performed 2x250bp sequencing at the V3-V4 region of the 16S rRNA gene using the MiSeq platform (Illumina, USA). We used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) to quantify the predicted functional abundance of the microbial composition referenced to the MetaCyc pathway database and investigated differences between pre-diet and post-diet microbial function pathways using longitudinal linear models for differential abundance (LinDA). Statistical significance was set at FDR p< 0.05.

Results: Participants were aged 43.3 ± 7.8 years and 70% female. Compared to predicted compositional function on the baseline diet, 19 pathways were upregulated, and three pathways were downregulated after following the WFKD for 8 weeks. Upregulated pathways were primarily related to enhanced metabolism in the urea cycle, methylglyoxal degradation, and synthesis of vitamin K. Pathways that were downregulated were related to N-glycosylation, creatinine degradation, and catechol degradation.

Conclusions: Our results suggest that the WFKD may alter the predicted function of microbial composition and provide preliminary evidence for potential gut-microbiome mediated metabolic pathways that could be targeted with WFKD interventions.

Funding Sources: This study was funded by the KUMC School of Health Professions Pilot Grant Award, the KUMC School of Health Professions PhD Student Research Award, and the KUMC Department of Dietetics and Nutrition.