Microbiome Insight: Microfluidic Single-Cell Imaging Platform to Map Probiotic Effects on Multi-Drug-Resistant Gut Pathogens

Microorganisms offer a unique and powerful platform for the development of innovative, targeted, and sustainable therapies in biomedicine, but this requires an understanding of their behavior in complex microenvironments. However, there is a lack of technologies that enable the study of a large number of bacterial strains under dynamic environmental conditions. We will therefore develop a unique platform for high-throughput analysis of microorganisms, enabling studies of pathophysiological and health-promoting processes within model microbiomes under fluctuating, natural conditions at the single-cell level. Hence, new microfluidic cultivation methods and AI-based imaging technologies with fluorescence and optoacoustic markers are being developed, which will provide new insights into the complexity of these microbial ecosystems. The analysis platform will be tailored to emulate relevant environmental conditions within the gut to investigate, e.g., the effects of probiotics, pathogens, or horizontal gene transfer on the gut microbiome pathophysiologies. Furthermore, oxygen-independent reporter proteins will enable species-specific labeling of probiotic and pathogenic bacteria, thus allowing real-time analysis of defined processes within microbial consortia using optical and optoacoustic imaging techniques. Therefore, we combine expertise from three Helmholtz research centers, the HZI (gut microbiome), the FZJ (microsystem engineering and smart real-time image analysis), and the HMGU (optoacoustic in vivo imaging), as well as the HHUD (synthetic microbiology). The project synergistically combines state-of-the-art biomedical imaging and engineering technologies, currently being developed within the Helmholtz, with new bioengineering strategies, translating these into a versatile technology platform for future clinical gut microbiome diagnostics and personalized therapies, such as for inflammatory bowel disease and colon cancer.