DESIGNING A HIGH-THROUGHPUT PLATFORM TO BIOPROSPECT THE HUMAN MICROBIOME AND MANIPULATE ITS INTERPLAY WITH HOST ENVIRONMENTS Project Summary The human microbiome, comprising hundreds of microbial species living in and on the body, is now recognized to play critical roles in human health and performance as well as disease prevention and management. A healthy microbiome (which has not yet been fully characterized because some key species cannot be cultured) keeps in check harmful microbes that are normally present. However, when this balance is perturbed, pathogenic microbes may overgrow, a condition called dysbiosis, and compromise both gut and immune functions. Development of technologies for the growth and manipulation of microbial consortia are urgently needed to assess the beneficial effects attributed to probiotics and synthetic communities. Developing such ability would enable clinicians to reverse microbial imbalance by providing a personalized set of microorganisms capable of restoring gut functions associated with infectious, inflammatory, metabolic, cardiovascular, and cognitive diseases in patients. To this end, my group aims to advance a bold and unique microfluidic-based technology to isolate, culture, reconstruct, and, in the long-term, manipulate the human gastrointestinal (GI, gut) microbiome to treat diseases. This application specifically aims to develop a nanoculture system to grow microbial isolates from the gut, including those as yet unculturable, and identify beneficial interactions or bioactive metabolites essential to design synthetic communities capable of eradicating or inhibiting the growth of pathogens such as Clostridium difficile. The preliminary effectiveness of the ‘designed’ communities will be determined by treating Clostridium difficile Infection (CDI) in an established mouse model. Our long-term goal is to develop a microbial bank of live biotherapeutics of human origin comprising defined microbial communities applicable for personalized and precision medicine. We envision this technology to be a safe, easy-to-deliver, and efficient alternative to fecal microbiota transplant (FMT) to treat diverse dysbiotic conditions, and thus help restore a healthy gut microbiome.

Project Narrative There is an urgent need to develop technologies for the growth and manipulation of microbial consortia to assess the beneficial effects attributed to some microorganisms and synthetic communities. Our long-term goal is to develop a microbial bank of live-biotherapeutics of human origin comprising defined microbial communities applicable for personalized and precision medicine. In the next pursuit of this goal, this investigation will develop a microfluidics-based human microbiome coculture platform to eradicate C. difficile infection and thereby restore a healthy microbiome.