Gut microbiome variation modulates the effects of dietary fiber on host metabolism

There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. Identifying the basis of this variation will enhance our understanding of microbe-diet-host interactions and may lead to novel personalized nutritional strategies. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, nevertheless, there were subtle richness and pronounced bacterial taxa abundance variations within each community among the different diet treatments. Host epigenetic, transcriptional and metabolomic analyses revealed diet-directed differences between microbiome groups, including variation in amino acids and lipid pathways, that were associated with divergent health outcomes. Overall, our results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy.