Probing Microbe-Material Interactions towards In situ Gut Microbiome Engineering

PART 1: NON-TECHNICAL SUMMARY

The human body is colonized by trillions of bacteria, fungi, protozoa and viruses; collectively referred to as the microbiome. The bacterial microbiome, particularly in the human gastrointenstinal tract, play critical roles in nutrient metabolism, immune training and prevention of infections. Yet, despite a clear link between the bacterial microbiome and human health, it remains difficult to determine the functional role each bacteria plays in human physiology and disease. This is largely due to a lack of accessible tools that allow researchers to carefully study and manipulate the microbiome composition within the gut. This project will study how microbes interact with biologic materials to improve the design of new materials-enabled tools for microbiome engineering. To achieve this, the team will explore the interactions of gut microbes with carbohydrate- and peptide-based biomaterials, determine how these microbe-material interactions alter microbiome communities, and utilize the insights gained to design new biomaterials that can control gut microbiome ecology. Findings from these studies will lead to a deeper understanding of how the microbes in our gastrointestinal tract interact with foreign materials, and in doing so yield transformative new biomaterial technologies that can be used to better study, diagnose and treat gut infections, disorders and diseases. Integration of this research program with the Penn State Center of Excellence in Industrial Biotechnology and the CSL Behring Fermentation Facility, which together educate students in the production of microbial-derived products, will engage and train a modern and diverse STEM workforce in emerging areas of materials science, glycobiology and microbial biotechnology.

PART 2: TECHNICAL SUMMARY

The overarching goal of this proposal is to establish a rational design framework for the development of biomaterials that can enable precision, in situ engineering of gut microbiome ecology. To achieve this, the research team will investigate the sequence-dependent interactions of probiotic microbes with carbohydrate- and peptide-based biomaterials, and elucidate how these microbe-material interactions shape the gut microbiome community. Fundamental to this work is the use of carbohydrate-peptide biocapsules, recently developed by the PI's lab, that can kill pathogens on contact and replace them with defined probiotic payloads. Using these materials as research platforms, this project will investigate how glycan composition and structure impacts microbial physiology, elucidate structure-activity relationships governing the bactericidal properties of polypeptide material coatings, and identify the physicochemical properties controlling the delivery of biocapsules to various gut compartments. Knowledge gained from this work will advance the development of biomaterials to probe and manipulate microbial ecology in the complex gastrointenstinal tract. Further, this work may identify the role biomaterials can play in manipulating the microbiome and their potential in advancing the design of new tailored bacteriotherapies against gut disorders. This research program will be integrated with the Penn State Center of Excellence in Industrial Biotechnology to offer unprecedented training opportunities for participating students at the interface of materials science, glycobiology and microbiology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.