There is supposedly a lot of potential in living bacterial therapeutics (LBT), which are assumed to have a positive influence on various pathophysiological processes from the microbiome. Numerous chronic human diseases, including obesity, non-alcoholic fatty liver disease, type 2 diabetes, atherosclerosis, polycystic ovary syndrome, inflammatory bowel disease, and cancer are targets for LBT in experimental medicine. However, despite the great creativity of experts in the field of synthetic biology, such strategies have so far only worked in model systems that are far removed from the real system, be it mice or humans. It almost always failed because the modified bacteria did not settle in the intestinal microbiome.