Synthetic Microbiomes on the Rise—Application in Deciphering the Role of Microbes in Host Health and Disease

The intestinal microbiota conveys significant benefits to host physiology. Although multiple chronic disorders have been associated with alterations in the intestinal microbiota composition and function, it is still unclear whether these changes are a cause or a consequence. Hence, to translate microbiome research into clinical application, it is necessary to provide a proof of causality of host–microbiota interactions. This is hampered by the complexity of the gut microbiome and many confounding factors. The application of gnotobiotic animal models associated with synthetic communities allows us to address the cause–effect relationship between the host and intestinal microbiota by reducing the microbiome complexity on a manageable level. In recent years, diverse bacterial communities were assembled to analyze the role of microorganisms in infectious, inflammatory, and metabolic diseases. In this review, we outline their application and features. Furthermore, we discuss the differences between human-derived and model-specific communities. Lastly, we highlight the necessity of generating novel synthetic communities to unravel the microbial role associated with specific health outcomes and disease phenotypes. This understanding is essential for the development of novel non-invasive targeted therapeutic strategies to control and modulate intestinal microbiota in health and disease.