Microbiome-mediated colonization resistance: defense against enteropathogens and multi-drug resistant organisms

Abstract

Gut colonization with multi-drug resistant organisms (MDROs) or enteropathogenic bacteria such as Clostridioides difficile can precede development of an infection and is considered an important public health concern. The gut microbiome is able to confer resistance against colonization and infection of such bacteria and this capability is termed colonization resistance. The aims of this thesis are 1) to recognize and identify bacteria or bacterial communities providing colonization resistance against enteropathogenic microorganisms and antibiotic resistant bacteria, and 2) to contribute to the microbiome research field by developing and applying new technical approaches. This thesis has been divided into three parts. First, current knowledge of microbiome-mediated colonization resistance against enteropathogens is summarized and supplemented with an overview of opportunities and challenges in development of new microbiome-based therapeutics. The second part of this thesis focuses on method optimization for microbiome research, both for wet-lab and dry-lab procedures. The final part describes changes in the human gut microbiota during infection or colonization by potentially pathogenic enteropathogens, including hookworm, C. difficile and MDROs.