MELiSSA (Micro-Ecological Life Support System Alternative) consists of a loop of interconnected bioreactors enabling the recycling of gas, liquid and solid wastes generated in a close environment using light as a source of energy. In terms of efficiency and safety, the risks undergone in case of a genetic evolution in the compartments are critical for the long term operation of this human-life-sustaining system. Next to natural evolution during years of continuous culturing, one must also take into account evolutionary changes owing to hostile environmental conditions that are experienced in deep space, i.e. outside the Earth's atmosphere. Therefore it will be necessary to monitor microbial robustness, horizontal gene transfer, genetic stability, and maintenance of the axenic conditions in the MELiSSA loop.