A new method to screen the gastrointestinal (GI) tract for radiation sensitivity and radiation-induced gene damage has a number of applications. This technology could be used to assess radiation susceptibility in individuals, such as astronauts, nuclear reactor workers, those undergoing radiation therapy for cancer, and others who may be or have been exposed. The method could also be used to develop and test various probiotic regimens to repopulate the GI tract microbiome to deliver more radiation resistance, or more rapid healing following radiation exposure.
Ionizing radiation, as well as certain commensal bacteria, can induce DNA damage associated with types of delayed cell cycles, thereby potentially protecting the host from epithelial injury. Complex chromosomal rearrangements and clustered DNA damage, along with cell cycle arrest, cell cycle delays at G1, and longer replication phases are possible risks for developing cancer, and can be specifically induced by galactic cosmic ionizing radiation. High linear energy transfer (LET) radiation, such as heavy charge and energy particles (HZE), or high-energy protons simulating a solar particle event, have been applied to the analysis in human fibroblasts and peripheral blood lymphocytes. Lethal doses of protons can cause high rates of apoptosis, and very high doses of ionizing radiation delivered by whole-body irradiation sterilize individual small intestine crypts. These types of ionizing radiation generate reactive oxygen species (ROS) by purine base oxidation and oxidative modification of sugar moieties towards unfavorable energetic states.
At nonlethal dose, radiation damage may accumulate after irradiation due to delays in DNA repair mechanism, pro-oncogenic proliferation, and subsequently occurring oxidative stress. Certain members of the microbiota termed “pathobionts” have pro-inflammatory activity such as activating invariant natural killer (NK) T cells and inducing Nod1 and Nod2 signaling. The intestinal microbiota was found to regulate endothelial radiosensitivity by suppressing fasting-induced adipose factor (Fiaf), which results in a loss of resistance through radiation-induced apoptosis in small intestines due to sterilization of mesenchymal stem cells.
Peroxidase activity in conventionally raised mice without radiation exposure but conventional and taxa-rich microbiota, has been associated with reduced tumorigenesis, reduced chronic ileocolitis, and apoptotic crypts. Probiotics, such as Lactobacillus species, but not conventional microbiota, have been shown to reduce radiation-induced small intestinal damage, Gram-negative bacteremia and endotoxemia, and watery stools or diarrhea. Lactobacillus johnsonii (LBJ) and probiotic DNA are known to require toll-like receptor (TLR) signaling, and specific Lactobacilli are associated with mediating anti-inflammatory effects. Organ-specific probiotics strains may exploit a distinctive apical TLR9-stimulated pathway of the innate immunity to regulate tolerance and inflammation, and cancer-associated inflammation by preventing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) activation. LBJ has been associated with an increase in the number of crypt Paneth cells, bactericidal activity, and therefore oxidative stress. However, probiotics — and specifically Lactobacilli species as well as Bifidobacteria, among others — were recently also reviewed for changing the native microbiota and reducing colorectal cancer.
The systemic effects of microbial composition were investigated on radiation-susceptibility and inflammatory-modulated oxidative DNA repair in a mouse model with restricted microbiota (RM), compared with mice with a conventional microbiota (CM). RM and CM mice have distinctive fecal microbiota (p<0.01, 16S ribosomal RNA (rRNA) pyrosequencing). Several taxonomic groups present in CM mice were absent or reduced in relative abundance in RM mice.
LBJ has been identified as being more abundant in RM microbiota composition than CM microbiota composition. A culturable bacterial strain has been isolated from RM individual mice, and both RM and CM mice were administered growing LBJ in buffered suspension before radiation exposure and for several days after radiation exposure. Whereas irradiated RM mice inoculated with LBJ also show very high levels of persistent DNA damage but no significant differences compared to non-inoculated and irradiated RM mice, CM mice administered LBJ do show an increase in persistent double-stranded DNA breaks after radiation exposure (compared to non-inoculated and irradiated CM mice). LBJ was given to these RM and CM mice at a dose that can be detected in their fecal samples. This finding clearly shows that genotoxic radiation-induced endpoints correlate with intestinal microbiota composition. A LBJ-rich microbiota mouse model is found to be radiation-susceptible, unaffected by apoptosis, and therefore reveals increased levels of persistent DNA damage after exposure to high-energy protons and ionizing radiation. Lactobacilli play an important role in the human gut microbiome. In particular, Lactobacillus johnsonii, acquired by the newborn as it passes through the birth canal, is said to have a role in helping newborns digest breast milk, but might also have an effect on the baby’s resistance to ambient ionizing radiation as well.
This work was done by Irene Maier and Robert Schiestl of the University of California, Los Angeles for Ames Research Center. NASA is seeking partners to further develop this technology through joint cooperative research and development. For more information about this technology and to explore opportunities, please contact David Morse at