Ionizing Radiation Dose Differentially Affects the Host–Microbe Relationship over Time
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals, and Veterinary Care
2.2. Total Body Gamma Irradiation Exposure and Monitoring Clinical Signs of Radiation
2.3. Sample Collection Post-Euthanasia
2.4. Descending Colon Contents 16S rRNA Gene Sequencing Assay
2.5. Untargeted Metabolomics of Descending Colon Contents
2.6. Quantitative Detection of Lipopolysaccharide Binding Protein (LBP) in Liver
2.7. Statistical Analysis and Data Integration
3. Results
3.1. Animal Health Status Following Lethal Doses of Ionizing Radiation
3.2. Descending Colon Contents’ Bacterial Diversity Showed Dose-Dependent Longitudinal Alterations
3.3. Shifts in Bacterial Abundances Depended on Radiation Dose and Time since Irradiation
3.4. Bionetworks Potentially Linked to Bacterial Shifted with Time since Irradiation
3.5. Descending Colon Contents’ Metabolite Expression Profile Shifted with Time since Irradiation
3.6. Differential Expression Analysis Identified Putative Early and Time-Independent Metabolite Markers of Irradiation
3.7. Regulation Profile of Metabolite-Enriched Networks Shifted Due to Radiation Dose and Time since Irradiation
3.8. LBP Loads in the Liver Samples Were Exclusively Increased by 11 Gy Irradiation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Day 1 | Day 3 | Day 9 | Day 1 | Day 3 | Day 9 | |||||||
Biofunctions’ Superfamily | Metagenome | Metabolome | Metagenome | Metabolome | Metagenome | Metabolome | Metagenome | Metabolome | Metagenome | Metabolome | Metagenome | Metabolome |
Amino acid metabolism | 4/1 | 0/0 | 0/0 | 3/2 | 1/2 | 1/0 | 3/2 | 0/0 | 3/1 | 4/0 | 3/2 | 0/0 |
Biosynthesis | 0/2 | 1/1 | 0/1 | 0/1 | 4/3 | 0/0 | 0/1 | 0/0 | 1/8 | 1/0 | 7/1 | 1/2 |
Bioenergy | 0/0 | 1/0 | 0/0 | 1/1 | 2/0 | 1/0 | 2/0 | 1/0 | 1/0 | 3/1 | 4/0 | 2/4 |
Immune functions | 0/0 | 0/0 | 0/0 | 7/1 | 0/0 | 0/3 | 0/0 | 0/1 | 0/0 | 2/0 | 1/0 | 0/3 |
Lipid metabolism | 1/0 | 0/4 | 0/0 | 6/1 | 0/0 | 2/4 | 1/1 | 0/0 | 2/2 | 0/1 | 2/0 | 0/9 |
Metabolite ID | Metabolite Name | Functional Relevance |
---|---|---|
All data points are consistently upregulated | ||
HMDB0240259 | Stercobilin/L-urobilin | A pro-inflammatory microbial metabolite, which is generated via the reduction in bilirubin by intestinal microbiota |
HMDB0001830 | Progesterone | Cancer-related metabolite and gut microbes metabolize and regulate the bioavailability of progesterone [55] |
HMDB0001898 | Mesobilirubinogen | Closely related to stercobilin, as they have the same parent compound, namely urobilinogen |
HMDB0006059 | 20-Carboxy-leukotriene B4 | An oxidized metabolite of leukotriene B4 (LTB4), which is released from polymorphonuclear granulocytes of severely burned patients |
HMDB0062552 | Goralatide | Protector of hematopoietic progenitors |
HMDB0060095 | Prostaglandin-c2 | Associated with inflammation [56] |
All but one data points are consistently upregulated | ||
HMDB0013200 | 5-Hydroxytryptophol glucuronide (GTOL) | A biomarker of alcohol load in body fluid [57] |
HMDB0031039 | Heptadecanal | Linked to smoking [58] |
HMDB0011563 | 1-pentadecanoylglycerol | -- |
HMDB0000054 | Bilirubin | Its elevation is linked to several diseases and disorders [59] |
All but one data points are consistently downregulated | ||
HMDB0011538 | 2-Linoleoylglycerol | -- |
HMDB0060987 | 2-Hydroxymethylolanzapine | Derivative of olanzapine, an atypical antipsychotic agent |
HMDB0000988 | S-Adenosylmethioninamine or dadomet | Linked to cancer [60] and psychotic deficiencies [61] |
HMDB0000860 | Phenylpropionylglycine | Associated with bacteria-driven metabolism [62] |
Early markers: Consistently upregulated at d1 and d3 post-TBI | ||
HMDB0001403 | Prostaglandin D2 (PGD2) | Associated with inflammation [56] |
HMDB0004161 | Urobilin | Generated through the degradation of heme |
HMDB0062389 | A sterol lipid molecule | A member to the class of cholesterols and derivatives |
HMDB0006888 | 5b-Cyprinol sulfate | An intermediate of bile acid biosynthesis |
Early markers: Consistently downregulated at d1 and d3 post-TBI | ||
HMDB0062251 | Alanine | A member to the class of an alanine or an alanine derivative |
HMDB0010727 | 3-Oxododecanoic acid | An intermediate in fatty acid biosynthesis |
HMDB0000860 | Phenylpropionylglycine | A fatty acid metabolite that could be a marker of mitochondrial dysfunction |
9.5 Gy | 11 Gy | |||||
---|---|---|---|---|---|---|
Subnetworks | d1 | d3 | d9 | d1 | d3 | d9 |
Flux of Ca+2 | Up | Up | Up | Up | Up | Up |
Synthesis of cAMP | Up | Up | Up | Up | Up | Up |
Metabolism of ROS | Down | Up | Down | Up | Up | Down |
Inflammatory response | Down | Down | Down | Down | Down | Down |
Conc. Of ATP | Down | Down | Down | Down | Down | Down |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Chakraborty, N.; Hoke, A.; Campbell, R.; Holmes-Hampton, G.; Kumar, V.P.; Moyler, C.; Gautam, A.; Hammamieh, R.; Ghosh, S.P. Ionizing Radiation Dose Differentially Affects the Host–Microbe Relationship over Time. Microorganisms 2024, 12, 1995. https://doi.org/10.3390/microorganisms12101995
Chakraborty N, Hoke A, Campbell R, Holmes-Hampton G, Kumar VP, Moyler C, Gautam A, Hammamieh R, Ghosh SP. Ionizing Radiation Dose Differentially Affects the Host–Microbe Relationship over Time. Microorganisms. 2024; 12(10):1995. https://doi.org/10.3390/microorganisms12101995
Chicago/Turabian StyleChakraborty, Nabarun, Allison Hoke, Ross Campbell, Gregory Holmes-Hampton, Vidya P. Kumar, Candace Moyler, Aarti Gautam, Rasha Hammamieh, and Sanchita P. Ghosh. 2024. "Ionizing Radiation Dose Differentially Affects the Host–Microbe Relationship over Time" Microorganisms 12, no. 10: 1995. https://doi.org/10.3390/microorganisms12101995
APA StyleChakraborty, N., Hoke, A., Campbell, R., Holmes-Hampton, G., Kumar, V. P., Moyler, C., Gautam, A., Hammamieh, R., & Ghosh, S. P. (2024). Ionizing Radiation Dose Differentially Affects the Host–Microbe Relationship over Time. Microorganisms, 12(10), 1995. https://doi.org/10.3390/microorganisms12101995