The continuous impact of radiation on organisms and the environment is one that is often colloquially ignored, lest a radioactive disaster takes place, nevertheless leading to a vastly misconceived conversation on the topic generally.
Radiation is close to omnipresent in our universe due to electromagnetic waves, often emitted as X-rays or gamma rays by radioisotopes that are generated through radioactive decay or produced through nuclear reactions. Isotopes such as Uranium-238, Potassium-40, Thorium-232 and their daughter products are constantly present in our environment, leading to continuous radiation exposure of all organisms on the planet. In addition to that, black-bodies such as the Sun, and other natural and anthropogenic processes in the Earth and the universe produce other forms of radiation such as UV and IR radiation. However, it is evident that some organisms are exposed to more radiation than others depending on their habitat, and certain organisms are able to thrive in extremely radioactive conditions. These aptly named radioresistant extremophiles are a class of organisms that have evolved to survive the adverse effects of excessive exposure to ionizing radiation.
In environments such as mountain ranges and open fields, it is quite common to observe the presence of bacteria such as Deinococcus radiodurans, who are capable of resisting supra-lethal doses of UV-radiation at intensities greater than 1000 J/m2. Likewise, species of Rhodanobacter and the microorganism Desulfuromans ferrireducens have been observed to survive in environments of high radioactivity, such as in nuclear waste-water.2 This ability of radioresistant extremophiles to survive high levels of radiation has been linked to their efficient DNA repair mechanisms and ability to produce protective primary (extremolytes) and secondary (extremozymes) metabolic products such as scytonemin, mycosporine-like amino acids, shinorine, porphyra-334, palythine, biopterin, and phlorotannin, among others.
This linkage of extremolytes and extremozymes to the resistance of radiation related adversities to organisms has enabled microbiologists and geneticists to investigate the utilization of these extremophiles in medical and biotechnological applications such as the production of useful anticancer drugs, antibiotics, therapeutics, and even in environmental applications such as the biodegradation of toxic and radioactive compounds, and in commercially impactful agricultural products.3
However, cutting edge research in biotechnology sees the study of gut microbiota for various purposes related to human health, such as the treatment of chronic diseases, boosting or regulating the immune system, and even investigations into the correlation of gut microbial processes and populations with the aging process in human beings. Due to the hot-potato nature of gut microbiota as a field of scientific study, naturally the utilization of these microbiota for radiation protection, radio-resistance and repair of damage to molecules and tissue due to excessive exposure to radiation is one that is being extensively researched on.
One of the main approaches to such radioprotection is through the use of existing probiotics with effects similar to those seen in extremophiles, such as Lactobacillus rhamnosus GG which modulates immune responses and protects the intestinal tissue from radiation-induced damage, and Bifidobacterium breve which enhances the mucosal barrier function and reducing inflammations. While these exist, it is undeniable that the use of genetically engineered probiotics would vastly benefit vulnerable humans such as in the recovery process of radiotherapy patients, and workers continuously exposed to excessive radiation.
The primary direction of the study of genetically engineering gut microbiota arises from a project titled MISS (Microbiome-Induced Space Suit) introduced in 2021, which investigates the ability of the genetic modification of microbiota to provide and enhance human resistance to ionizing radiation, specifically in manned space missions, as the exposure to ionizing radiation in space is extremely high.4 The method concerns the tailored production of enzymes and antioxidants, which can be used to mitigate and potentially reverse damage to DNA, thereby promoting the repair mechanisms of targeted cells and tissue through enabling the precise delivery of therapeutic molecules or the modulation of specific cellular pathways.5,6 This, in turn, could be used as alternatives for existing intrusive methods such as hormone therapy, which requires continuous drug administration. The MISS project is currently being researched on, and it aims to achieve this monumental objective through two major approaches.
The first approach involves identifying the specific molecular mechanisms that allow humans to tolerate high exposure to radiation without negative health effects by locating the expression of unique genes, regulatory pathways, and protein functions that are regulated in these populations. Once this is done, the human microbiome could be modified to recreate the protective effects witnessed in populations exposed to excessive radiation.
The second approach involves use of the DNA damage suppressor protein (DSUP), whose major role is to protect DNA from radiation damage and oxidative stress, where the objective lies in the modification of this protein, or the use of molecules homologous to it, so that its effects are observed in levels of radiation well above the lethal radiation dose of humans.4
While this study specifically focuses on the final goal of constructing a space suit, the fundamental principle of its function and role could be easily extended to more applicable scenarios such as in the case of radiotherapy patients. The MISS project has sparked a large curiosity and drive towards meeting the demand for radiation protection mechanisms in humans, and while genetic modification of gut microbiota is a relatively new topic of concern, the potential of its advancement of our understanding of human health has garnered it an almost cult-like following of researchers and industry experts.
It can therefore be concluded, with no large surprise, that the topic of probiotic engineering for radiation protection would continue to be discussed for several years to come.
References
- Anagnostakis, M. J. (2015). Environmental radioactivity measurements and applications–difficulties, current status and future trends. Radiation Physics and Chemistry, 116, 3-7.
- Green, S. J., Prakash, O., Jasrotia, P., Overholt, W. A., Cardenas, E., Hubbard, D., … & Kostka, J. E. (2012). Denitrifying bacteria from the genus Rhodanobacter dominate bacterial communities in the highly contaminated subsurface of a nuclear legacy waste site. Applied and environmental microbiology, 78(4), 1039-1047.
- Gabani, P., & Singh, O. V. (2013). Radiation-resistant extremophiles and their potential in biotechnology and therapeutics. Applied microbiology and biotechnology, 97(3), 993-1004.
- Yakimova, A. O., Nikolaeva, A., Galanova, O., Shestakova, V. A., Smirnova, E. I., Levushkina, A., … & Klabukov, I. D. (2024). Microbiota-Induced Radioprotection: A Novel Approach to Enhance Human Radioresistance with In-Situ Genetically Engineered Gut Bacteria. Applied Microbiology, 5(1), 1.
- Li, P., Roos, S., Luo, H., Ji, B., & Nielsen, J. (2023). Metabolic engineering of human gut microbiome: recent developments and future perspectives. Metabolic Engineering, 79, 1-13.
- Barra, M., Danino, T., & Garrido, D. (2020). Engineered probiotics for detection and treatment of inflammatory intestinal diseases. Frontiers in Bioengineering and Biotechnology, 8, 265.