This gene editing of the gut microbiota provides a way to study the role bacterial genes play in disease and health. The microbiota is considered an important modulator of human health and disease. The intestinal, or gut, microbiota, is the richest and most complex microbiota ecosystem in the body. It provides many beneficial functions such as educating our immune systems, synthesizing essential vitamins and nutrients, and fending off invading pathogens. However, the gut microbiota is sensitive to environmental changes such as medications, stress, or diet. Studies have shown these changes to the microbiota environment could promote diseases such as digestive disease, arthritis, asthma, cardiovascular disease, neurological disorders and cancer. Scientists are unable to study the different microbiota genes functionally linked to these diseases because more than 90% of the bacteria forming in the microbiota are not genetically amendable by current gene editing techniques, such as flp recombinase, transposon, or chemical screen. This poses a severe obstacle in scientists’ abilities to conduct mechanistic studies of microbiota function in disease, preventing the development of therapeutic treatments. New tools must be employed to alter bacterial genomes to open the way for novel therapeutics.
Researchers at the University of Florida can manipulate or silence specific gut microbiota through exosome-mediated siRNA. Scientists around the world will have the ability to design functional experiments targeting specific genes. They will be able to provide critical information about the role of microbiota in various biological processes and diseases, opening the way for therapeutics using precision medicine for microbiota.
Mechanism for specific gene silencing in the gut microbiota, allowing for the study of the role bacterial genes have on human health and disease
This gene editing system utilizes a transkingdom communication network between mammals and bacteria. The mammalian sRNAs are processed and loaded into the RNA Induced Silencing Complex (RISC). Gene expression is either silenced (siRNA) or repressed (miRNA) following the recognition of the sRNA to its’ target. These are then packaged into an exosome, loaded with the RNA Induced Silencing Complex, and purified, before being added to a bacterial genome to silence specific genes. In addition, the RNA Induced Silencing Complex can be programmed to target a specific gene before being introduced in the bacteria.