Skip to main content
NUTRITION 2025 Main banner

President's Oral Session: Abstracts of Distinction

(OR14-03-25) Metabolic Plasticity of the Gut Microbiome in Response to Diets Differing in Glycemic Load in a Random Crossover Design Intervention

Monday, June 2, 2025
10:24 AM - 10:36 AM ET
Location: S230 CD
Objectives: The objective of this analysis was to evaluate the effect of a low glycemic load (LGL) compared to high glycemic load (HGL) dietary pattern on gut bacterial community structure and metabolism in a randomized cross-over controlled feeding study in healthy men and women (n=80).

Methods: Each diet was fed for 28 days, separated by at least a 28-day washout. The LGL diet provided GL of 125 and the HGL diet provided a GL of 250. Fasting (12-hour) blood draws were collected on days 1 and 28 of each feeding period, processed and immediately stored at -80°C for biomarker analyses (HOMA IR). We extracted genomic DNA and total RNA from paired stool samples taken at the end of each dietary period. Metatranscriptomic and metagenomic sequencing (HiSeq) and bioinformatic analysis (HUMAnN2 and Carbohydrate Active Enzyme (CAZymes) were analyzed. RNA/DNA for functional pathways and carbohydrate enzymes were used in linear regression models, adjusted for age, DXA-assessed body fat, energy intake, diet order, and sex (n=64).

Results: HOMA IR on the HGL and LGL diets were 2.4 (1.8) and 2.5 (2.2), respectively, and not significantly different. Overall community structure was not significantly different across the diets although diet did significantly increase the abundance of 21 species (q < 0.05). Differential expression analysis showed that on the HGL diet, the hexitol fermentation pathway was significantly enriched (q=1.82E-03, β=-1.15). On the LGL diet, expression of the lysine biosynthesis pathway was significantly enriched (q=0.03, β=0.21) and starch degradation was borderline enriched (q=0.09, β=0.27). The number and composition of carbohydrate enzymes varied between diets (MiRKAT, p< 0.001). The expression of CAZymes enriched in the HGL diet reflected food additives while CAZymes enriched in the LGL diet reflected diverse phytochemical intake. Microbial fatty acid metabolism was positively associated with a marker of insulin resistance (HOMA-IR) in the refined-grain diet (Pantothenate and CoA biosynthesis, q =0.035).

Conclusions: In healthy humans, diet impacts microbial metabolism and enzymatic activity but not the overall diversity of the gut microbiome showing the relevance of dietary components in activating certain bacterial gene expression and its impact on host metabolism, possibly linked to HOMA-IR.

Funding Sources: National Institute of Health