Journal of Radiation Protection and Research

The Korean Association for Radiation Protection (대한방사선방어학회)
권호 표지
DOI QR코드

DOI QR Code

Short-Term Changes in Gut Microflora and Intestinal Epithelium in X-Ray Exposed Mice

  • Received : 2020.08.31
  • Accepted : 2020.11.28
  • Published : 2020.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Gut microflora contributes to the nutritional metabolism of the host and to strengthen its immune system. However, if the intestinal barrier function of the living body is destroyed by radiation exposure, the intestinal bacteria harm the health of the host and cause sepsis. Therefore, this study aims to trace short-term radiation-induced changes in the mouse gut microflora-dominant bacterial genus, and analyze the degree of intestinal epithelial damage. Materials and Methods: Mice were irradiated with 0, 2, 4, 8 Gy X-rays, and the gut microflora and intestinal epithelial changes were analyzed 72 hours later. Five representative genera of Actinobacteria, Firmicutes, and Bacteroidetes were analyzed in fecal samples, and the intestine was pathologically analyzed by Hematoxylin-Eosin and Alcian blue staining. In addition, DNA fragmentation was evaluated by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results and Discussion: The small intestine showed shortened villi and reduced number of goblet cells upon 8 Gy irradiation. The large intestine epithelium showed no significant morphological changes, but the number of goblet cells were reduced in a radiation dose-dependent manner. Moreover, the small intestinal epithelium of 8 Gy-irradiated mice showed significant DNA damaged, whereas the large intestine epithelium was damaged in a dose-dependent manner. Overall, the large intestine epithelium showed less recovery potential upon radiation exposure than the small intestinal epithelium. Analysis of the intestinal flora revealed fluctuations in lactic acid bacteria excretion after irradiation regardless of the morphological changes of intestinal epithelium. Altogether, it became clear that radiation exposure could cause an immediate change of their excretion. Conclusion: This study revealed changes in the intestinal epithelium and intestinal microbiota that may pave the way for the identification of novel biomarkers of radiation-induced gastrointestinal disorders and develop new therapeutic strategies to treat patients with acute radiation syndrome.

Keywords

References

  1. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837-848. https://doi.org/10.1016/j.cell.2006.02.017
  2. Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in't Veld JH. Overview of gut flora and probiotics. Int J Food Microbiol. 1998;41:85-101. https://doi.org/10.1016/S0168-1605(98)00044-0
  3. Flint HJ, Duncan SH, Scott KP, Louis P. Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc. 2015;74:13-22. https://doi.org/10.1017/S0029665114001463
  4. Fay KT, Ford ML, Coopersmith CM. The intestinal microenvironment in sepsis. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt B):2574-2583. https://doi.org/10.1016/j.bbadis.2017.03.005
  5. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3-20. https://doi.org/10.1016/j.jaci.2009.05.038
  6. Camilleri M, Madsen K, Spiller R, Greenwood-Van Meerveld B, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil. 2012;24:503-512. https://doi.org/10.1111/j.1365-2982.2012.01921.x
  7. Ribet D, Cossart P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect. 2015;17:173-183. https://doi.org/10.1016/j.micinf.2015.01.004
  8. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol. 2016;16:639-649. https://doi.org/10.1038/nri.2016.88
  9. Dainiak N, Waselenko JK, Armitage JO, MacVittie TJ, Farese AM. The hematologist and radiation casualties. Hematology Am Soc Hematol Educ Program. 2003;2003:473-496. https://doi.org/10.1182/asheducation-2003.1.473
  10. Ding LH, Shingyoji M, Chen F, Hwang JJ, Burma S, Lee C, et al. Gene expression profiles of normal human fibroblasts after exposure to ionizing radiation: a comparative study of low and high doses. Radiat Res. 2005;164:17-26. https://doi.org/10.1667/RR3354
  11. Ishii T, Futami S, Nishida M, Suzuki T, Sakamoto T, Suzuki N, et al. Brief note and evaluation of acute-radiation syndrome and treatment of a Tokai-mura criticality accident patient. J Radiat Res. 2001;42 Suppl:S167-182. https://doi.org/10.1269/jrr.42.S167
  12. Anno GH, Baum SJ, Withers HR, Young RW. Symptomatology of acute radiation effects in humans after exposure to doses of 0.5- 30 Gy. Health Phys. 1989;56:821-838. https://doi.org/10.1097/00004032-198906000-00001
  13. Yang SH, Yang RS, Tsai CL. Septic arthritis of the hip joint in cervical cancer patients after radiotherapy: three case reports. J Orthop Surg (Hong Kong). 2001;9:41-45. https://doi.org/10.1177/230949900100900209
  14. Yamanouchi K, Tsujiguchi T, Sakamoto Y, Ito K. Short-term follow-up of intestinal flora in radiation-exposed mice. J Radiat Res. 2019;60:328-332. https://doi.org/10.1093/jrr/rrz002
  15. International Atomic Energy Agency. Diagnosis and treatment of radiation injuries. Vienna, Austria: International Atomic Energy Agency; 1998.
  16. Bartosch S, Fite A, Macfarlane GT, McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004;70:3575-3581. https://doi.org/10.1128/AEM.70.6.3575-3581.2004
  17. Rinttila T, Kassinen A, Malinen E, Krogius L, Palva A. Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J Appl Microbiol. 2004;97:1166-1177. https://doi.org/10.1111/j.1365-2672.2004.02409.x
  18. Potten CS, Merritt A, Hickman J, Hall P, Faranda A. Characterization of radiation-induced apoptosis in the small intestine and its biological implications. Int J Radiat Biol. 1994;65:71-78. https://doi.org/10.1080/09553009414550101
  19. Somosy Z, Horvath G, Telbisz A, Rez G, Palfia Z. Morphological aspects of ionizing radiation response of small intestine. Micron. 2002;33:167-178. https://doi.org/10.1016/S0968-4328(01)00013-0
  20. Otsuka K, Suzuki K. Differences in radiation dose response between small and large intestinal crypts. Radiat Res. 2016;186:302-314. https://doi.org/10.1667/RR14455.1
  21. Daly MJ. A new perspective on radiation resistance based on Deinococcus radiodurans. Nat Rev Microbiol. 2009;7:237-245. https://doi.org/10.1038/nrmicro2073
  22. Daly MJ, Gaidamakova EK, Matrosova VY, Vasilenko A, Zhai M, Leapman RD, et al. Protein oxidation implicated as the primary determinant of bacterial radioresistance. PLoS Biol. 2007;5:e92. https://doi.org/10.1371/journal.pbio.0050092
  23. Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr. 2002;22:283-307. https://doi.org/10.1146/annurev.nutr.22.011602.092259
  24. Nishiyama K, Ochiai A, Tsubokawa D, Ishihara K, Yamamoto Y, Mukai T. Identification and characterization of sulfated carbohydrate-binding protein from Lactobacillus reuteri. PLoS One. 2013;8:e83703. https://doi.org/10.1371/journal.pone.0083703
  25. Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002;82:279-289. https://doi.org/10.1023/A:1020620607611
  26. Servin AL, Coconnier MH. Adhesion of probiotic strains to the intestinal mucosa and interaction with pathogens. Best Pract Res Clin Gastroenterol. 2003;17:741-754. https://doi.org/10.1016/S1521-6918(03)00052-0