Model-guided Engineering of Complex Microbial Communities

Microbial communities occupy practically all habitats on Earth, from ocean deeps to the human gut, and are pivotal to the ecosystem function. They also hold a vast biotechnological potential to realize functionalities typically beyond the reach of single species, e.g. valorisation of complex resources. Rational design and modulation of communities can thus help addressing outstanding challenges in health and bio-sustainability. Yet, this remains difficult due to the complexity of interspecies interactions. Towards tackling this, I plan to combine modelling, genetics, omics and laboratory evolution to study complex microbial communities with a focus on metabolic cross-feeding. Kefir, a natural milk-fermenting community, and stable assemblies of human gut bacteria will be used as two model systems. Both systems have recently been pioneered by my lab and represent complexity relevant for real-world applications. We will first investigate the genetic and environmental factors driving metabolite secretion using high-throughput screening of natural isolates and genetic libraries. Large-scale pairwise interaction mapping and self-establishing stable sub-communities will be used to unravel higher-order interactions and to discover the principles of community assembly. Laboratory evolution will then be used to assess community stability as well as to decipher interaction mechanisms through multi-omics analyses. The experimental data on species metabolism and interspecies interactions will be used to build hybrid metabolic-ecological models for predicting effects of perturbations like species introduction and nutrient change. The applicability will be demonstrated through stable introduction of probiotic species in personalized gut bacterial communities, and by developing vitamin overproducing milk fermenting communities. The results will have fundamental implications for modulating microbial communities relevant for environment, health and biotechnology.