Organizational principles of the human microbiome and their applications in fecal microbiota transplantation --- An ecological and functional network-based study

A variety of microbial communities exist throughout the human body, which play a crucial role in determining our health and well-being. Microbiome-based therapies that aim to shift a disrupted microbiome of a patient into a healthy state for improving his/her clinical condition are developing boomingly. However, since the microbiome is an extremely complex and dynamic ecological system, we need to fully understand its organizational features and principles in order to rationally and precisely design its manipulations, such as fecal microbiota transplantation (FMT). In the proposed research, we will systematically investigate two fundamental principles required in order to lead a stable alteration of the microbiome state based on the ecological dynamic networks and functional genomic content networks: (1) The microbiome ecosystem of healthy subjects has natural resilience, i.e., it tends to return to its original state after a perturbation. Therefore, in order to gain a long-term shift of the microbiome, we need to understand the origins of the resilience. (2) Even if the FMT succeeds to change the original microbiome state, we need to be able to predict its long-term stabilization post-FMT. Otherwise, the new unpredicted microbiome state might be ineffective or even detrimental. The proposed research will improve our understanding on the organizational principles of the human microbiome toward developing personalized and stable fecal microbiota transplantation.