Host and intestinal microbiota derived metabolomic blood plasma signature for prior radiation injury

1. A kit for determining a dose of radiation that a subject has been exposed to, the kit comprising:

a mass spectrometer for quantifying a concentration of each metabolite in a plurality of metabolites;

a receptacle into which a body fluid sample from the subject is placed, and which is connectable to the mass spectrometer so that the mass spectrometer can measure the concentration of each metabolite of the plurality of metabolites in the sample;

a non-transitory computer-readable medium coupled to one or more data processing apparatus having instructions stored thereon which, when executed by the one or more data processing apparatus, cause the one or more data processing apparatus to perform a method for determining the dose of radiation that the subject has been exposed to by implementing an algorithm on a data set comprising the concentration of each metabolite of the plurality of metabolites in the sample so as to determine the dose of radiation that the subject has been exposed to by correlating the concentration of each metabolite of the plurality of metabolites with the received dose of radiation;

a visual display and/or audible signal that indicates the dose of radiation that the subject has been exposed to, wherein the dose of radiation that the subject has been exposed to is determined to be only one of:

1 to 2 Gy;

2 to 4 Gy;

4 to 6 Gy;

6 to 8 Gy;

or greater than 8 Gy, and

wherein the plurality of metabolites consists of:

Thymidine

2′-Deoxyuridine

2-Aminobutyrate

2-Hydroxyisobutyrate

1-Eicosadienoylglycerophosphocholine

2-Palmitoylglycerophosphocholine

Ectoine

Homocitrulline

3-Hydroxypropanoate

Citrulline

1-Arachidonoylglycerophosphoethanolamine

Equol glucuronide

3-Phenyl propionate (hydrocinnamate)

Stachydrine

1-Palm itoleoylglycerophosphocholine

chiro -Inositol

Docosahexaenoate (DHA22:6n3)

gamma-Glutamylisoleucine

1-Arachidonoylglycerophosphoinositol

Eicosapentaenoate (EPA20:5n3)

Pipecolate

Dihomo-linolenate (20:3n3 or n6)

1-Myristoylglycerophosphocholine

2-Linoleoylglycerophosphoethanolamine

Salicylate

Phenol sulfate

N-acetylhistidine

4-Vinylphenol sulfate

1-Linoleoylglycerophosphoethanolamine

3-Indoxyl sulfate

p-Cresol sulfate

Indolelactate

1-Linoleoylglycerophosphoinositol

Homostachydrine

1-Palm itoylglycerophosphoinositol

Equol sulfate; and

Indolepropionate.

2. The kit of claim 1 , wherein the plurality of metabolites includes metabolites arising from at least one intestinal microbiota within the subject.

3. The kit of claim 1 , wherein the body fluid sample is selected from the group consisting of blood, plasma, or another a blood derivative.

4. The kit of claim 1 , wherein the subject is a human subject.

5. A method of determining a dose of radiation that a subject has been exposed to, comprising:

a) quantifying a concentration of each metabolite of a plurality of metabolites in a sample, wherein the sample is selected from the group consisting of blood, plasma, or another a blood derivative;

b) implementing an algorithm on a data set comprising the quantified concentrations of each metabolite of the plurality of metabolites so as to obtain an algorithm output;

c) correlating the algorithm output with the dose of radiation that the subject has been exposed to so as to determine the dose of radiation that the subject has been exposed to, wherein the dose of radiation that the subject has been exposed to is only one of

1 to 2 Gy;

2 to 4 Gy;

4 to 6 Gy;

6 to 8 Gy;

or greater than 8 Gy, and

wherein the plurality of metabolites consists of the following metabolites:

Thymidine

2′-Deoxyuridine

2-Aminobutyrate

2-Hydroxyisobutyrate

1-Eicosadienoylglycerophosphocholine

2-Palm itoylglycerophosphocholine

Ectoine

Homocitrulline

3-Hydroxypropanoate

Citrulline

1-Arachidonoylglycerophosphoethanolamine

Equol glucuronide

3-Phenyl propionate (hydrocinnamate)

Stachydrine

1-Palm itoleoylglycerophosphocholine

chiro -Inositol

Docosahexaenoate (DHA22:6n3)

gamma-Glutamylisoleucine

1-Arachidonoylglycerophosphoinositol

Eicosapentaenoate (EPA20:5n3)

Pipecolate

Dihomo-linolenate (20:3n3 or n6)

1-Myristoylglycerophosphocholine

2-Linoleoylglycerophosphoethanolamine

Salicylate

Phenol sulfate

N-acetylhistidine

4-Vinylphenol sulfate

1-Linoleoylglycerophosphoethanolamine

3-Indoxyl sulfate

p-Cresol sulfate

Indolelactate

1-Linoleoylglycerophosphoinositol

Homostachydrine

1-Palm itoylglycerophosphoinositol

Equol sulfate; and

Indolepropionate.

6. The method of claim 5 , wherein the plurality of metabolites arises from the subject and from at least one intestinal microbiota of the subject.

7. The method of claim 5 , wherein the body fluid sample is blood plasma.

8. The method of claim 5 , wherein the method is performed within 24 hours after the subject is exposed to the dose of radiation.

9. The method of claim 5 , wherein the method is performed within 48 hours after the subject is exposed to the dose of radiation.

10. The method of claim 5 , wherein the concentrations of each metabolite of the plurality of metabolites are quantified using a mass spectrometer.

11. A system comprising:

one or more data processing apparatus; and

a non-transitory computer-readable medium coupled to the one or more data processing apparatus having instructions stored thereon which, when executed by the one or more data processing apparatus, cause the one or more data processing apparatus to perform a method for determining a dose of radiation that a subject has been exposed to, comprising:

a) quantifying a concentration of each metabolite in a plurality of metabolites in a sample obtained from the subject, wherein the plurality of metabolites consists of:

Thymidine

2′-Deoxyuridine

2-Aminobutyrate

2-Hydroxyisobutyrate

1-Eicosadienoylglycerophosphocholine

2-Palmitoylglycerophosphocholine

Ectoine

Homocitrulline

3-Hydroxypropanoate

Citrulline

1-Arachidonoylglycerophosphoethanolamine

Equol glucuronide

3-Phenyl propionate (hydrocinnamate)

Stachydrine

1-Palmitoleoylglycerophosphocholine

chiro -Inositol

Docosahexaenoate (DHA22:6n3)

gamma-Glutamylisoleucine

1-Arachidonoylglycerophosphoinositol

Eicosapentaenoate (EP A20: 5n3)

Pipecolate

Dihomo-linolenate (20:3n3 or n6)

1-Myristoylglycerophosphocholine

2-Linoleoylglycerophosphoethanolamine

Salicylate

Phenol sulfate

N-acetylhistidine

4-Vinylphenol sulfate

1-Linoleoylglycerophosphoethanolamine

3-Indoxyl sulfate

p-Cresol sulfate

Indolelactate

1-Linoleoylglycerophosphoinositol

Homostachydrine

1-Palmitoylglycerophosphoinositol

Equol sulfate

Indolepropionate;

b) implementing an algorithm on a data set that comprises the concentrations of each metabolite in the plurality of metabolites so as to obtain an algorithm output;

c) determining the dose of radiation that the subject has been exposed to after implementing the algorithm output, wherein the dose of radiation that the subject has been exposed to is only one of:

1 to 2 Gy;

2 to 4 Gy;

4 to 6 Gy;

6 to 8 Gy;

or greater than 8 Gy.