Effects of Combined Bacterial Infection and Radiation Injury on Biofluid Metabolite Profiles in the Murine Model

Evan L Pannkuk1,2,3, Anika Kot1, Lorreta Yun-Tien Lin1

  • 1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, D.C., District of Columbia 20057, United States.

ACS Omega
|November 3, 2025
PubMed

Insights

Assessing radiation exposure with Listeria infection requires advanced biodosimetry. This study shows a metabolomics model combining serum and urine accurately predicts radiation dose and infection status in mice.

Area of Science:

  • * Radiation biology
  • * Infectious disease
  • * Metabolomics

Background:

  • * Rapid biodosimetry is crucial for assessing radiation exposure, especially when complicated by secondary infections.
  • * Listeria monocytogenes infection can confound existing biodosimetry methods.
  • * Evaluating the impact of infection on metabolite-based biodosimetry is essential for accurate dose assessment.

Purpose of the Study:

  • * To investigate how Listeria monocytogenes infection affects metabolite profiles in serum and urine.
  • * To develop and validate a biodosimetry model that accounts for radiation exposure and bacterial infection.
  • * To assess the accuracy of a multivariate random forest model for predicting radiation dose and infection status.

Main Methods:

  • * Male C57BL/6 mice were infected with Listeria monocytogenes and exposed to 0, 2, or 6 Gy X-rays.
  • * Untargeted metabolomics was performed on serum and urine samples collected one day post-irradiation.
  • * A multivariate random forest analysis was used to build a predictive model using combined biofluid data.

Main Results:

  • * Listeria infection increased white blood cell counts and altered metabolite signatures in serum and urine.
  • * Specific serum lipids and urinary TCA intermediates were affected by infection alone.
  • * A combined biofluid model accurately predicted radiation dose and infection status with 90% accuracy (RMSE = 1.31 Gy).

Conclusions:

  • * Metabolite-based biodosimetry can be adapted to account for confounding factors like Listeria infection.
  • * A multiplexed biodosimetry panel using serum and urine metabolites shows promise for accurate dose assessment in complex scenarios.
  • * These findings support the development of robust biodosimetry tools for improved triage decisions in radiological emergencies.

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