Metabolic plasticity of the gut microbiome in response to diets differing in glycemic load in a randomized, crossover, controlled feeding study.

Background: Dietary patterns characterized by low-glycemic, minimally processed plant foods are associated with lower risk of several chronic diseases.

Objective: Evaluate the effects of a low glycemic load (LGL) versus a high glycemic load (HGL) dietary pattern on stool bacterial community structure and metabolism.

Methods: Participants in this crossover-controlled feeding study were healthy men and women (n=69). We identified genera, species, and genes and transcripts of metabolic pathways and bacterial enzymes using 16S rRNA gene, metagenomic and metatranscriptomic sequencing, and bioinformatic analysis.

Results: Overall community structure measured by alpha and beta diversity were not significantly different across the diets although diet did significantly increase the abundance of 13 out of 161 genera (p_adj<0.05) and 5 species in the LGL and 7 species in the HGL diet. Gene expression in the hexitol fermentation pathway (β=-1.15, SE=0.24 with 95% CI (-1.63, -0.67); p_adj=0.002) was significantly higher in the HGL diet, whereas expression in the L-lysine biosynthesis pathway (β =0.20, SE=0.05 with 95% CI (0.09, 0.30); p_adj=0.03); was enriched in the LGL diet. The beta diversity of expressed carbohydrate-active enzymes (CAZymes) was significantly different between the diets (MiRKAT, p<0.001). CAZymes enriched in the HGL diet reflected dietary additives while CAZymes enriched in the LGL diet reflected diverse phytochemical intake. There was a significant interaction between HOMA IR and the Coenzyme A biosynthesis I pathway involved in bacterial fatty acid biosynthesis (p_adj=0.035) that was positive in the HGL diet (β=0.20, SE=0.09 with 95% CI (0.02, 0.39)) and negative in the LGL diet (β =-0.23, SE=0.09 with 95% CI (-0.40, -0.06)).

Conclusion: In healthy humans, diet impacts microbial metabolism and enzymatic activity but not the overall diversity of the gut microbiome. This emphasizes the relevance of dietary components in activating expression of specific bacterial genes and their impact on host metabolism. This trial was registered at clinicaltrials.gov as NCT00622661.