Host-microbe-diet interplay: Dietary modulation of the gut microbiota in relation to health.

摘要

Vertebrates are associated with trillions of bacteria, with the densest populations residing in the large intestine. The symbiosis between vertebrates and their gut microbiota has resulted in important implications of the gut microbiome on host health. Diet is an important factor that shapes gut microbiota composition, and because of the interplay between host-microbiome-diet, dietary strategies that modulate gut microbiome structure are deemed a relevant tool to improve host health. However, gaps in knowledge exist with respect to these interactions, and it is essential to obtain a mechanistic understanding of how these relations take place to develop successful therapeutic strategies that target the gut microbiome.;In order to address these gaps, human trials were performed to assess the impact of primary components of the human diet, resistant starches and whole grains, on the gut microbiota. Overall, the impact of diet was temporal and varied across subjects. Resistant starches substantially modulated the gut bacterial community of the subject population, especially increasing the abundance of Bifidobacterium adolescentis. Ruminococcus bromii, Eubacterium rectale, and Parabacteroides distasonis were also significantly enriched. Dietary incorporation of whole grains increased the proportions of Eubacterium rectale and acetogens such as Blautia wexlerae. Of note, whole grains significantly improved inflammation and glycemic parameters. The shifts in Eubacterium rectale correlated with glycemic improvements. Moreover, distinct abundances of Dialister were determined among subjects that differed in terms of their inflammatory improvement.;To gain mechanistic insight on the host-microbe-diet interplay, animal experiments were conducted to evaluate the effects of grain sorghum lipids and plant sterol esters in the context of dyslipidemia. Significant and consistent alterations in gut microbiota composition were detected in both experiments, especially involving shifts in Coriobacteriaceae and Erysipelotrichaceae abundance, which displayed remarkable correlations to host cholesterol markers. Mathematical modeling of these associations revealed them to be inhibitory interactions, suggesting that changes in host metabolism affected gut microbiome structure through an antimicrobial effect of cholesterol, which was conformed in vitro against selected gut microbes.;In conclusion, the studies presented in this dissertation allowed new insights on the impact of diet on the gut microbiota and its consequences for health.