Design and development of a recombinant probiotic for the prevention of antibiotic-mediated dysbiosis

The human gut microbiota, consisting of a coherent mixture of commensal microorganisms, is responsible for a number of vital functions that aid in the support and protection of the human body. The disruption of the homeostasis of the microbiota, also known as dysbiosis, can therefore lead to extensive consequences, affecting the biology in the gut. Consequently, this can lead to or affect (long-lasting) metabolic, immunological, and developmental disorders, as well as infectious diseases. Although a multitude of factors may be involved in such diseases, research has supported the significant role of antibiotic use, and rather its consequences. The “collateral damage” caused by antibiotic administration has demonstrated its potential in permanently affecting the composition of the microbiota due to the antibiotic residues reaching the colon. We are therefore in urgent need of a solution that protects patients from the damage caused by antibiotic use and ensures the functionality of antibiotics themselves on the long-run. In this study, we evaluated the potential of an antibiotic degrading yeast probiotic with unique features that prevent the transfer of functional enzymes to the commensal flora. To this end, we created 25 different DNA constructs (44 different yeast strains) with five different antibiotic degrading enzymes. With in vitro and ex vivo data we demonstrate the potential of such a versatile biological system that may have clinical application as a life biotherapeutic product (LBP) in the prevention of antibiotic-mediated dysbiosis.