The effect of modulation of gut microbiome profile on radiation-induced carcinogenesis and survival

Author:

Cook John A1,Sowers Anastasia L1,Choudhuri Rajani1,Gadisetti Chandramouli2,Edmondson Elijah F3,Gohain Sangeeta1,Krishna Murali C1,Mitchell James B1

Affiliation:

1. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute , Bethesda MD 20892 , USA

2. GenEpria Consulting Inc. Columbia , MD 21046 , USA

3. Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research , Frederick, MD 21702 , USA

Abstract

Abstract Non-lethal doses of ionizing radiation (IR) delivered to humans because of terrorist events, nuclear accidents or radiotherapy can result in carcinogenesis. Means of protecting against carcinogenesis are lacking. We questioned the role of the gut microbiome in IR-induced carcinogenesis. The gut microbiome was modulated by administering broad spectrum antibiotics (Ab) in the drinking water. Mice were given Ab 3 weeks before and 3 weeks after 3 Gy total body irradiation (TBI) or for 6 weeks one month after TBI. Three weeks of Ab treatment resulted in a 98% reduction in total 16S rRNA counts for 4 out of 6 of the phylum groups detected. However, 3 more weeks of Ab treatment (6 weeks total) saw an expansion in the phylum groups Proteobacteria and Actinobacteria. The Ab treatment altered the bacteria diversity in the gut, and shortened the lifespan when Ab were administered before and after TBI. Mortality studies indicated that the adverse Ab lifespan effects were due to a decrease in the time in which solid tumors started to appear and not to any changes in hematopoietic or benign tumors. In contrast, when Ab were administered one month after TBI, lifespan was unchanged compared to the control TBI group. Use of broad-spectrum antibiotics to simulate the germ-free condition did not afford an advantage on carcinogenesis or lifespan.

Funder

Medical Countermeasures against Radiological and Nuclear Threats Program

National Institute of Allergy and Infectious Diseases

National Institutes of Health and the Intramural Research Program

Center for Cancer Research

National Cancer Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology, Nuclear Medicine and imaging,Radiation

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