Gut microbiota-mediated impacts of dietary fiber deprivation in gnotobiotic mice and healthy humans

A growing number of diseases have been linked to aberrations in the interaction between diet, gut microbiota, and host immune function. Understanding these complex dynamics will be critical for the development of personalized therapeutic regimens to improve health outcomes. In mice colonized with a defined, 14-member synthetic human microbial community, mucin-degrading bacteria proliferate and are suspected to contribute to thinning of the colonic mucus layer and enhanced pathogen susceptibility. This dissertation investigates three aspects of diet–microbiome–host interactions in healthy models. In the first chapter, we investigate this question in early life by assessing the impact of the maternal microbiota and fiber-deprivation on immune development in pups. Next, we leverage an adult mouse model to ascertain the effects of specific fiber types on bacterial metabolic output and host immunity. Finally, we translate this work into humans by examining the effects of a high- and low-fiber diet on host mucolytic bacteria populations and early inflammatory shifts in healthy adults. Interim analyses indicate that there is high translatability of the mouse findings to humans, with similar changes in composition and enzymatic activities according to fiber intake. By implementing a bench-to-bed-to-bench research approach, this work aims to expand the range of commensals that can be considered as potential biomarkers of early barrier disruption or targeted using customized diet-based approaches.