K. Kort

Eco-evolutionary dynamics and control of the gut microbiome

The intestinal tracts of human and other animals hosts a highly diverse, dynamic and personalised community of microbes that plays a vital role in regulating digestion, immunity and health. Recent next-generation metagenomic sequencing efforts have provided an unprecedented view of the species composition of the gut microbiota, its development over life, and the way it adjusts in response to changes in diet or lifestyle. Moreover, abnormal microbiota have been associated with several diseases, including cancer, chronic inflammatory bowel diseases and psychiatric disorders. Currently, however, we lack a mechanistic understanding of the processes that shape the diversity and ecological interactions within the microbial community, which makes it difficult to intervene in a targeted way to improve the function of the gut microbiota by means of pre- or probiotics.

Here we propose a research project aimed at developing a computational eco-evolutionary framework for modelling the microbiome. This framework builds on genome-scale models of microbial metabolism to quantify the fluxes of metabolites between microbial species, the gut environment, and the host, in order to reconstruct the ecological interactions within the microbial community. We will characterise the ecological assembly rules of the microbial community, investigate whether the feedback between metabolic fluxes and community assembly can explain the presence of alternative stable community states, and study how to induce transitions between such alternative stable states. We will also investigate the process of coevolution between microbial species, study under what conditions evolution of the microbiota aligns with the interests of the hosts and explore mechanisms to direct evolution towards an improved ecosystem functioning. Insights from these ecological and evolutionary analysis will be applied to a model of microbial imbalance in patients suffering from inflammatory bowel disease, with the aim of identifying novel targets for pre- and probiotic treatment.