Submitted Abstract
General awareness of the microbiome and its relationship to human health and disease has grown in recent years and today attracts major interest from the global pharmaceutical, nutritional and biotechnological industries. Driven by technological innovations, the growing depth of microbiome knowledge has dissected associations between specific microbial communities and different pathological conditions and diseases. In this context the Eco-Systems Biology research group at the Luxembourg Centre for Systems Biomedicine has recently developed a novel microfluidics-based human-microbial co-culture system – HuMiX. HuMiX is a model of the human gastrointestinal interface which allows for the systematic investigation of molecular interactions between the host and the microbial cells in vitro. The HuMiX technology is already protected by a strong patent portfolio and has been developed under the funding support of Fonds National de la Recherche through an FNR CORE Programme Grant, an FNR Accompany Measures grant and an FNR INTER Mobility Grant. Various molecular pathways have been characterized in recent years that might mediate the effects of microbiota on metabolism, the immune system and drug treatment outcomes. The mutual regulation between the intestinal microbiome and the host is an emerging area in biomedical research and it is poised to transform the pharmaceutical and nutraceutical industries. A better understanding of the interaction between the microbiome and the gut will lead to the development of new guidelines for personalized treatment, help to improve global human health, and establish ways to prevent and treat various diseases via personalized pharmaceutical and/or dietary interventions. Most of the data published in the field of microbiome science and its interaction with the components of the human gut are based on murine studies commonly using knockout or germ-free animals. Their relevance in human biology requires validation using specific, personalized human models. Although HuMiX has proved its scientific value in tackling the interaction of human gastrointestinal cell lines with certain bacterial strains, we are still lacking a comprehensive model system, which allows, in a high-throughput fashion, the standardized employment of primary immune cells, individual-derived epithelial cells and specific microbial communities. Thus, we wish to develop the new upgraded iHuMiX to become the first personalized in vitro model to investigate the interactions between immune, epithelial and bacterial cells. We aim to use iHuMiX for testing the efficacy of drugs as well as dietary compounds to address a clear industrial demand and meet the needs of a developing market on the edge of microbiome science, immunology, oncology and nutrition sectors. iHuMiX will involve the co-culture of individual-derived microbiota, enterocytes and immune cells and will thereby result in personalized in vitro models for studying responses to different drug and diet regimes. This PoC project will focus on the development of the iHuMiX model as a tool for discovery of microbiome-derived biomarkers, drug targets and bioactive molecules and as a potential companion in the diagnostics and therapeutics used in the physiology and pathology of the gut. We aim to participate in the rapidly advancing science of the gut microbiome, thus we already have developed strategic collaborations with academic and industrial partners, such as RIKEN, Nestlé, NextCure and InceptionScience for customer validation and to gain the necessary market approval for the technology. The goal is to create and to contribute to the development of dedicated service platform based on the iHuMiX technology in Luxembourg, whereby we will have the capability to reliably handle service requests from the pharmaceutical and nutraceutical industries for compound screening and discovery.