Interactions between the human milk oligosaccharide 2’-fucosyllactose and Bifidobacterium species influence colonization in complex gut communities

Bifidobacterium taxa are associated with the breastfed infant gut, namely, due to the bifidogenic nature of human milk’s oligosaccharide fraction. This association provides a model of resource-driven microbial assemblies as human milk oligosaccharides (HMO) are accessible to microbes found in the infant gut but the infant cannot use HMO as a nutrient resource. The catabolism strategy (intracellular versus extracellular) and breadth of HMO structures utilized by a Bifidobacterium microbe impacts fitness and competitive nature in a microbial community. Previous work focused on profiling Bifidobacterium genetic diversity and in vitro metabolism of human milk oligosaccharides (HMO). Chapter 1, a mini-review, attempts to synthesize research, focusing on how functional capabilities provide a fitness advantage to certain Bifidobacterium species when applied to an infant gut. The addendum contains primary research on how Bifidobacterium pseudocatenulatum strains forage for fucosylated HMO.The principal goal of this dissertation was to understand if a Bifidobacterium population could be enriched in a complex microbial community and if persistence could be achieved through introduction of an HMO nutrient resource, 2’-fucosyllactose (2’FL). Chapter 2 introduces how supplementation of 2’FL provides a fitness advantage to a Bifidobacterium pseudocatenulatum strain possessing a fucosylated HMO gene cluster in a mouse model. Even when high colonization resistance was present, 2’FL, a privileged nutrient resource, facilitated persistence and ameliorated a DSS-induced colitis model. Chapter 3 further characterizes the Bifidobacterium pseudocatenulatum persistence mouse model. Bifidobacterial metabolite products from 2’FL catabolism were found locally and systemically, although enrichment of those metabolites was dependent on high levels of B. pseudocatenulatum persisting in the mouse gut. This study also introduces the concept of mice categorized as responders and non-responders in this work. Additional Bifidobacterium species were tested for persistence in a mouse model. These strains evaluated hypotheses surrounding catabolism strategies and the necessity of HMO utilization genes. In Chapter 4 subjects were categorized as responder and non-responder depending on Bifidobacterium persistence success, which was varied. This variance could not be determined by the presence of any one bacterial taxa at baseline. However, future studies could assess the functional capacity of the baseline microbiota to test if certain niches were open in mice categorized as responders. This work furthers our understanding of Bifidobacterium strain-specific fitness differences in complex microbial communities. When choosing bacterial species with the objective of persistence or engraftment, researchers should first understand the molecular mechanisms for resource capture and catabolism, and the baseline microbial community’s functional capabilities