Method for determining the distinctive nutritional requirements of a patient

1. A method for manufacturing a nutritional composition for administration to a subject suffering from an inflammatory bowel disease characterized by distinctive nutritional requirements in the subject over a healthy subject, the method comprising:

a. determining in a sample of the subject suffering from the inflammatory bowel disease a profile of statuses of markers comprising direct and indirect markers indicating the nutritional profile of the subject, wherein each of the direct markers indicates an amount of a macronutrient or micronutrient, and each of the indirect markers are derived from the direct markers by quantifying a corresponding direct marker and quantifying one or more additional markers that indicate a status of the corresponding direct marker, at least one of the direct and indirect markers is selected from the group consisting of an amino acid marker, a fat marker, a carbohydrate marker, a nucleotide marker, an osmolyte marker, a peptide marker, a catabolism marker, a nitric synthase marker, and combinations thereof;

b. determining in a sample of the healthy subject a profile of the statuses of the same markers comprising the same direct and indirect markers determined in step a, at least one of the sample of the subject suffering from the inflammatory bowel disease or the sample of the healthy subject is a sample selected from the group consisting of whole blood, blood plasma, blood serum, red blood cells, urine, tissue biopsies, and combinations thereof;

c. comparing the profiles determined in steps a. and b., and determining distinctive nutritional requirements for nutrients comprising macronutrients and micronutrients in the subject suffering from the inflammatory bowel disease based on the comparison of the profiles determined in steps a. and b., wherein when a level of the markers determined in step a. is lower than a level of the same markers determined in step b., the distinctive nutritional requirements for the subject comprise a composition comprising the nutrients in an effective amount to enable a level of the nutrients in the subject suffering from the inflammatory bowel disease to match a level of the nutrients in the healthy subject; and

d. manufacturing the composition comprising the nutrients in the effective amount to restore the nutritional profile of the nutrients in the subject suffering from the inflammatory bowel disease to or toward that of the healthy subject as determined in step b.

2. The method according to claim 1 , wherein in step a., the statuses of the markers is determined in a cohort of subjects suffering from IBD.

3. The method according to claim 1 , wherein in step b., the statuses of the markers is determined in a cohort of healthy subjects.

4. The method according to claim 1 , wherein the statuses of at least 10 markers are determined.

5. The method according to claim 1 , wherein the catabolism marker is selected from the group consisting of ammonia, urea, monomethyl, dimethylarginine, and combinations thereof.

6. The method according to claim 1 , wherein the markers further comprise an oxidative stress marker selected from the group consisting of 4-hydroxynonenal, malondialdehyde, nitrotyrosine, carbonylated proteins, total glutathione, reduced glutathione, oxidized glutathione, glutathione peroxidase activity, glutathione reductase activity, superoxide dismutase activity, catalase activity, and combinations thereof.

7. The method according to claim 1 , wherein the nitric synthase marker is selected from the group consisting of nitrite, nitrate, monomethyl arginine, asymmetric dimethylarginine, symmetric dimethylarginine, arginine, citrulline, ornithine, argininosuccinic acid, and combinations thereof.

8. The method according to claim 1 , wherein the amino acid marker comprises a marker of an amino acid selected from the group consisting of amino alanine, β-alanine, sarcosine, arginine, monomethylarginine, assymetric-dimethylarginine, symmetric dimethylarginine, asparagine, aspartic acid, citrulline, glutamic acid, glutamine, glycine, histidine, 1-methylhistidine, 3-methylhistidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, hydroxyproline, ethanolamine, α-aminobutyric acid, β-aminoisobutyric acid, γ-aminobutyric acid, homocysteine, cysteine, γ-glutamyl-cysteine, cysteinyl-glycine, homocystine, cysteine, cystathionine, methionine sulfoxide, selenomethionine, methionine sulfoximine, selenocysteine, selenocystine, ergothioneine, N-formyl-L-methionine, S-adenosylhomocysteine, or S-Adenosylmethioninamine, alpha-ketobutyric acid, 2-aminobutyric acid, 2-amino-3-ketobutyric acid, alpha-keto-beta-methylbutyric acid (or alpha-ketoisovaleric acid), alpha-ketoisocaproic acid, or alpha-keto-beta-methylvaleric acid, and combinations thereof.

9. The method according to claim 1 , wherein the markers further comprise a fatty acid marker selected from the group consisting of butyric C4:0, caproic C6:0, caprilic C8:0, capric C10:0, undecanoic C11:0, lauric C12:0, tridecanoic C13:0, myristic C14:0, pentadecanoic C15:0, palmitic C16:0, heptadecanoic C17:0, stearic C18:0, arachidic C20:0, heneicosanoic C21:0, behenic C22:0, lignoceric C24:0, myristoleic C14:1 n-5, cis-10-Pentadecenoic C15:1 n-5, palmitoleic C16:1 n-7, cis-10-heptadecenoic C17:1 n-7, elaidic C18:1 n-9 trans, oleic C18:1 n-9 cis, cis-11-Eicosenoic C20:1 n-9, erucic C22:1 n-9, nervonic C24:1 n-9, linoelaidic C18:2 n-6 trans, linoleic C18:2 n-6 cis, gamma-linolenic C18:3 n-6, alpha-Linolenic C18:3 n-3, cis-11,14-Eicosadienoic C20:2 n-6, cis-8,11,14-eicosatrienoic C20:3 n-6, cis-11,14,17-eicosatrienoic 20:3 n-3, arachidonic C20:4 n-6, cis-13,16-docosadienoic 22:2 n-6, cis-5,8,11,14,17-eicosapentanoic (EPA) C20:5 n-3, cis-4,7,10,13,16,19-Docosahexaenoic (DHA) C22:6 n-3 acid, lipoic acid, and combinations thereof.

10. The method according to claim 1 , wherein the markers further comprise an element marker of an element selected from the group consisting of lithium (Li), boron (B), magnesium (Mg), aluminium (Al), silicon (Si), phosphorous (P), sulfur (S), potassium (K), calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), bromine (Br), rubidium (Rb), strontium (Sr), molybdenum (Mo), tin (Sn), iodine (I), barium (Ba), titanium (Ti), sodium (Na), chlorine (Cl), and fluorine (F).

11. The method according to claim 1 , wherein the markers further comprise a vitamin marker of a vitamin or a metabolite thereof selected from the group consisting of vitamin B1, vitamin B2, vitamin B3, nicotinamide, methylnicotinamide, nicotinuric acid, choline, vitamin B5, vitamin B6, pyridoxal phosphate, pyridoxic acid, vitamin B8, vitamin B9, methyl tetrahydrofolic acid, vitamin B12, hydroxycobalamin, adenosylcobalamin, and combinations thereof.

12. The method of claim 1 , wherein the nucleotide marker comprises a marker of a nucleotide selected from the group consisting of inosine 5′monophosphate, adenosine 5′monophosphate, cytidine 5′monophosphate, guanosine 5′-monophosphate, inosine 5′monophosphate, uridine 5′monophosphate, and combinations thereof.

13. The method of claim 1 , wherein the osmolyte marker is selected from the group consisting of trimethylamine N-oxide, dimethylsulfoniopropionate, trimethylglycine, sarcosine, betaine, glycerophosphorylcholine, myo-inositol, and combinations thereof.

14. The method of claim 1 , wherein the markers further comprise a phytonutrient marker of a phytonutrient selected from the group consisting of carotenoids, ellagic acid, flavonoids, chlorogenic acids, resveratrol, glucosinolates, phytoestrogens, or a combination thereof.

15. The method according to claim 1 , wherein the peptide marker comprises a marker of a peptide selected from the group consisting of reduced gluthathione, oxidized glutathione, and combinations thereof.

16. A method for treating a human subject suffering from an inflammatory bowel disease characterized by distinctive nutritional requirements in the human subject over a healthy subject, the method comprising:

a. determining in a sample of the human subject suffering from the inflammatory bowel disease a profile of statuses of direct and indirect markers indicating the nutritional profile of the human subject, wherein each of the direct markers indicates an amount of a macronutrient or micronutrient, and each of the indirect markers are derived from the direct markers by quantifying a corresponding direct marker and quantifying one or more additional markers that indicate a status of the corresponding direct marker, at least one of the direct and indirect markers is selected from the group consisting of an amino acid marker, a fat marker, a carbohydrate marker, a nucleotide marker, an osmolyte marker, a peptide marker, a catabolism marker, a nitric synthase marker, and combinations thereof;

b. determining in a sample of the healthy subject a profile of the statuses of the same markers comprising the same direct and indirect markers determined in step a, at least one of the sample of the subject suffering from the inflammatory bowel disease or the sample of the healthy subject is a sample selected from the group consisting of whole blood, blood plasma, blood serum, red blood cells, urine, tissue biopsies, and combinations thereof;

c. comparing the profiles determined in step a. and b., and determining distinctive nutritional requirements for nutrients comprising macronutrients and micronutrients in the human subject suffering from the inflammatory bowel disease based on the comparison of the profiles determined in steps a. and b., wherein when a level of the markers determined in step a. is lower than a level of the same markers determined in step b., the distinctive nutritional requirements for the subject comprise a composition comprising the nutrients in an effective amount to enable a level of the nutrients in the subject suffering from the inflammatory bowel disease to match a level of the nutrients in the healthy subject;

d. providing the composition to restore the nutritional profile of the nutrients in the human subject suffering from the inflammatory bowel disease; and

e. administering the composition to the human subject suffering from the inflammatory bowel disease.

17. The method according to claim 1 , wherein the indirect marker is selected from the group consisting of combinations of nutrients and micronutrients, biomarkers of nutrients or micronutrients, metabolites of nutrients or micronutrients, catabolites of nutrients or micronutrients, physiological states, ratios between nutrients and micronutrients, ratios between micronutrients, determinations of functional markers, and combinations thereof.

18. The method according to claim 17 , wherein the functional markers comprise measurement of an activity selected from the group consisting of erythrocyte transketolase activity, erythrocyte glutathione reductase activity, oxidative stress status, nitric oxide synthase activity, and combinations thereof.