Microbiota-Induced Radioprotection: A Novel Approach to Enhance Human Radioresistance with In-Situ Genetically Engineered Gut Bacteria

The high sensitivity of living organic forms to space radiation remains the critical issue during spaceflight, to which they will be chronically exposed during months of interplanetary or even decades of interstellar spaceflight. In the human body, all actively dividing and poorly differentiated cells are always close to being damaged by radiological or chemical agents. The chronic exposure to ionizing radiation primarily causes changes in blood counts and intestinal damage such as fibrosis, obliterative vasculitis, changes in the gut microbiota, and atrophy or degeneration of muscle fibers. The project “MISS: Microbiome Induced Space Suit” was presented at the Giant Jamboree of the International Genetically Engineered Machine Competition 2021, with the aim to investigate the ability of the novel microbiota-mediated approach to enhance human resistance to ionizing radiation. The key innovative part of the project was the idea to create a novel radioprotector delivery mechanism based on human gut microbiota with the function of outer membrane vesicles (OMVs) secretion. The project concept proposed the feasibility of genetically modifying the human microbiota in situ through the delivery of genetic constructs to the host's crypts using silicon nanoparticles with chemically modified surfaces. In this perspective, we discuss the advances in modifying microbiota-mediated secretory activity as a promising approach for radioprotection and as an alternative to hormone therapy and other health conditions that currently require continuous drug administration. Future clinical trials of in situ methods to genetic engineering the crypt microbiota may pave the way for indirect regulation of human cells.