ABSTRACT

Some bacteria are beneficial to their host. These are referred to as probiotics. Taking a supplement containing these organisms may be a way to treat diseases like obesity, diabetes, or heart disease. The gut already contains a wide variety of microbes, but introducing new ones that remain in place is difficult. This research project aims to implement and evaluate a two-step strategy to create an environment suitable for successfully introducing probiotics. The first step is to modify the probiotics so that they can use nutrients not normally found in the gut. The second step is to introduce the probiotic and the unusual nutrient (referred to as a prebiotic) to the gut. The working hypothesis is that this combination will provide a unique environment in which the target probiotic can thrive. This work will advance knowledge of the role of nutrients in regulating the gut ecosystem, drug delivery by engineered probiotics, and the usage of prebiotics in the human diet. This research project also supports the development of an interactive laboratory in which students will be able to observe competition between engineered gut bacteria.

The goal of this research project is to create a niche for engineered probiotic bacteria through the use of unique prebiotics. The first objective is to understand the effect that introducing prebiotics has on microbial communities in vitro and in vivo. The second objective is to create unique prebiotic-probiotic pairs by in vitro protection and in vivo deprotection of engineered prebiotics. Microbial populations in simulated cultures and in mice supplemented with an array of prebiotics will be characterized. Those results will guide the design of prebiotics that can provide maximal advantage to the probiotics. Novel nutrients will be generated by enzymatic and/or chemical modification of existing prebiotics. Probiotic strains will be engineered to express enzymes that undo these protective modifications to enable utilization. The results of this research project could have significant positive impacts on the engineering of beneficial microbiomes in outdoor environments as well as inside humans and animals.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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