UC San Diego

Gut dysbiosis can have an impact on a host’s susceptibility to disease due to the human reliance on microbial functions. Due to the major effects of the gut microbiome on various aspects of human health, there is a need to better understand the mechanisms behind what creates a healthy microbiome and how a microbiome can transition to a diseased state. Synthetic microbial gut communities have been previously developed as a method to better understand microbial interactions and functions, but most of them consisted of only a small number of species with a limited ability to model the complexity of the gut. One recent study incorporated 119 different strains from the most prevalent taxa in the human gut into a synthetic community but displayed an imbalanced final composition between fast and slow-growing strains, reducing its efficacy in representing slow-growing strains that are necessary for microbiome function. With the findings from previous studies in mind, this master’s thesis focuses on the development of a reproducible synthetic community with high complexity and a balanced composition named hCom as a study of how the human gut microbiome functions. This project aims to establish a model of the gut microbiome with increased α-diversity that allows for the study of both fast and slow-growing strains by incorporating the individual rates of change of growth for each strain into the design of the community. To assemble the community, four groups were made by separating the strains based on their rates of change of growth and added to the community at a 10-fold difference in concentration between each group. Upon analyzing the final composition of the community, it was found that the hCom design did successfully increase the relative-abundance of slow-growing strains while decreasing the relative-abundance of fast-growing strains, however one genus with medium-slow growing strains demonstrated dominance over the community, thus reducing the overall balance. Altogether the results of this thesis were successful in achieving its research goal of reducing the dropout of slow-growing strains, but there is still more work to be done in creating an even composition of the microbial community. By continuing to improve on the composition of the community, the information learned from experiments on the hCom can be applied to the native gut microbiome and the host-microbiome relationship, as well as aid in the development of treatments for human disease in the future.