Engineered Probiotics for Detection and Treatment of Inflammatory Intestinal Diseases

Abstract

Inflammatory intestinal diseases such as Crohn’s disease and ulcerative colitis have seen an increase in their prevalence in developing countries throughout the current decade. These are caused by a combination of genetic and environmental factors, altered immune response, intestinal epithelium disruption and dysbiosis in the gut microbiome. Current therapies are mainly focused on treating symptoms and are often expensive and ineffective in the long term. Recently, there has been an increase in our understanding of the relevance of the gut microbiome and its impact on human health. Advances in the use of probiotics and synthetic biology have led to the development of intestinal biosensors, bacteria engineered to detect inflammation biomarkers, that work as diagnostic tools. Additionally, live biotherapeutics have been engineered as delivery vehicles to produce treatment in situ avoiding common complications and side effects of current therapies. These genetic constructs often express a therapeutic substance constitutively, but others could be regulated externally by specific substrates, making the production of their treatment more efficient. Additionally, certain probiotics detecting specific biomarkers in situ and responding by generating a therapeutic substance are beginning to be developed. While most studies are still in the laboratory stage, a few modified probiotics have been tested in humans. These advances indicate that live biotherapeutics could have great potential as new treatments for inflammatory intestinal diseases.