Arjama Roy, Amity University Kolkata
The toxicity of ionizing radiation has been known for almost as long as ionizing radiation itself. High-dose radiation is related to the induction of chronic as well as acute radiation syndromes which may be further characterized into hematopoietic, gastrointestinal, and cerebrovascular syndromes. The intestine is the prime place for gut microbiota as it is the major target of radiation.
Gut microbes, also as microbe-derived metabolites represented by short-chain fatty acids (SCFAs) and tryptophan metabolites, have essential roles in regulating host metabolism and immunity. SCFAs and tryptophan metabolites reduce pro-inflammatory cytokines like tumor necrosis factor-a, interleukin-6, and interferon-g and promote the anti-inflammatory cytokines. These are all vital mediators of radiation-induced damage.
A recent study published in the Science journal showed that certain “elite” mice, when exposed to total body radiation, were protected against the radiation damage. Researchers found an abundance of two types of bacteria- Lachnospiraceae and Enterococcaceae in their gut after radiation. Unbiased microbiome analysis was done where Lachnospiraceae and Enterococcaceae were identified as the most enriched bacteria in elite-survivors. It was found Lachnospiraceae and Enterococcaceae in promoting hematopoiesis and attenuating gastrointestinal damage. In humans, leukemia patients were found to be abundant with these two types of bacteria.
The study showed that the presence of the two bacteria led to an increased production of small molecules called propionate and tryptophan. These metabolites provide long-term protection from radiation, lessened damage to bone marrow vegetative cell production, mitigated the event of severe gastrointestinal problems and reduced damage to DNA. Further, an untargeted metabolomics study revealed a realm of metabolites that were tormented by radiation and selectively increased in elite-survivors. Among them, 1 H-indole-3-carboxaldehyde (I3A) and kynurenic acid (KYNA), are the two tryptophan pathway metabolites that provided long-term radioprotection in vivo.
This finding has emphasized an important role for the gut microbiota as a master regulator of host defense against radiation, capable of protecting both the hematopoietic and gastrointestinal systems. It also highlights the crucial role that the microbiota metabolite axis plays in generating broad protection against radiation and provides promising therapeutic targets to treat the adverse side effects of radiation exposure.
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Source: Hao Guo, Wei-Chun Chou, Yunjia Lai, Kaixin Liang, Jason W. Tam, W. June Brickey, Liang Chen, Nathan D. Montgomery, Xin Li, Lauren M. Bohannon, Anthony D. Sung, Nelson J. Chao, Jonathan U. Peled, Antonio L. C. Gomes, Marcel R. M. van den Brink, Matthew J. French, Andrew N. Macintyre, Gregory D. Sempowski, Xianming Tan, R. Balfour Sartor, Kun Lu, Jenny P. Y. Ting. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites. Science, 2020; 370 (6516): eaay9097 DOI: 10.1126/science.aay9097
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