title: An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis.
abstract: Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo. The gastrointestinal (GI) system is of particular importance in radiation biodosimetry due to its constant cell renewal and sensitivity to radiation-induced injury. While the clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are manifested after radiation exposure, no reliable bioindicator has been identified for radiation-induced gastrointestinal injuries. To this end, we focused on determining a fecal metabolomic signature in X-ray irradiated mice. There is overwhelming evidence that the gut microbiota play an essential role in gut homeostasis and overall health. Because the fecal metabolome is tightly correlated with the composition and diversity of the microorganism in the gut, we also performed fecal 16S rRNA sequencing analysis to determine the changes in the microbial composition postirradiation. We used in-house bioinformatics tools to integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut integrated ecosystem and its deviations from a stable host-microbiome state that result from irradiation. The 16S rRNA sequencing results indicated that radiation caused remarkable alterations of the microbiome in feces at the family level. Increased abundance of common members of Lactobacillaceae and Staphylococcaceae families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic data revealed statistically significant changes in the microbial-derived products such as pipecolic acid, glutaconic acid, urobilinogen and homogentisic acid. In addition, significant changes were detected in bile acids such as taurocholic acid and 12-ketodeoxycholic acid. These changes may be associated with the observed shifts in the abundance of intestinal microbes, such as R. gnavus , which can transform bile acids.
authors: a   Department of Biochemistry and Molecular and Cellular Biology and.
authors: Maryam
authors: M
authors: Goudarzi
authors: c   Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, Maryland;
authors: Tytus D
authors: TD
authors: Mak
authors: d   Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and.
authors: Jonathan P
authors: JP
authors: Jacobs
authors: a   Department of Biochemistry and Molecular and Cellular Biology and.
authors: Bo-Hyun
authors: BH
authors: Moon
authors: a   Department of Biochemistry and Molecular and Cellular Biology and.
authors: Steven J
authors: SJ
authors: Strawn
authors: d   Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and.
authors: Jonathan
authors: J
authors: Braun
authors: e   Center for Radiological Research, Columbia University, New York, New York.
authors: David J
authors: DJ
authors: Brenner
authors: a   Department of Biochemistry and Molecular and Cellular Biology and.|b   Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC;
authors: Albert J
authors: AJ
authors: Fornace
authors: a   Department of Biochemistry and Molecular and Cellular Biology and.
authors: Heng-Hong
authors: HH
authors: Li
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000528:radiation effects*; D011832:Radiation Injuries / Q000378:metabolism* / Q000382:microbiology*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D001647:Bile Acids and Salts