Materials and methods for improving gastrointestinal function
The subject invention provides therapeutic compositions, and uses thereof for the treatment or amelioration of injury to small intestine mucosa. In preferred embodiments, the composition comprises one or more nutrients and/or electrolytes that acquire or retain considerable absorptive capacity.
1. A composition for improving small intestine health, wherein the composition is formulated for enteral administration and comprises threonine, valine, tryptophan, serine, and tyrosine, as free amino acids; and water; wherein the composition does not comprise free amino acid glutamine or a glutamine-containing dipeptide, or, if free amino acid glutamine and/or a glutamine-containing dipeptide is present, the total concentration of the free amino acid glutamine and the glutamine-containing dipeptide is less than 50 mg/l; wherein the composition does not comprise glucose or, if glucose is present, the concentration of glucose is less than 1 g/l; and wherein the composition does not comprise free amino acid methionine or a methionine-containing peptide.
2. The therapeutic composition according to claim 1 , wherein the composition does not comprise fructose.
3. The therapeutic composition according to claim 1 , further comprising lysine, glycine, aspartic acid, and/or isoleucine.
4. The therapeutic composition according to claim 1 , wherein the composition does not comprise glucose, and glutamine.
5. The composition, according to claim 1 , wherein the composition further comprises electrolytes, vitamins, minerals, and/or flavoring agents.
6. A method for treating a subject having villous atrophy, wherein the method comprises administering to the subject, via enteral administration, a composition formulated for enteral administration, wherein the composition comprises threonine, valine, tryptophan, serine, and tyrosine, as free amino acids, and water; wherein the composition does not comprise free amino acid glutamine or a glutamine-containing dipeptide, or, if free amino acid glutamine and/or a glutamine-containing dipeptide is present, the total concentration of the free amino acid glutamine and the glutamine-containing dipeptide is less than 50 mg/l; wherein the composition does not comprise glucose or, if glucose is present, the concentration of glucose is less than 1 g/l; and wherein the composition does not comprise free amino acid methionine or a methionine-containing dipeptide.
7. The method according to claim 6 , wherein the subject is a human.
8. The method according to claim 6 , wherein the subject has at least a 5% reduction in total number of small intestinal epithelial cells in the villous region, when compared to normal.
9. The method according to claim 6 , wherein the subject has at least a 5% loss in villous height in the small intestine, when compared to normal.
10. The method according to claim 6 , wherein the composition further comprises lysine, glycine, aspartic acid, and/or isoleucine.
11. The method according to claim 6 , wherein the composition does not comprise glucose, glutamine and glutamine-containing dipeptides.
12. The method according to claim 6 , wherein the villous atrophy is caused by disease, radiation, chemotherapy, proton therapy, abdominal surgery, and/or a cytotoxic agent.
13. The method according to claim 12 , wherein the composition is administered for a period of 1 to 14 days after the subject receives radiation, chemotherapy, proton therapy, or a cytotoxic agent.
14. The method according to claim 12 , used to treat villous atrophy caused by radiation enteritis.
15. The method according to claim 12 , used to treat villous atrophy caused by chemotherapy or cytotoxic agents selected from cisplatin, 5-fluorouracil (5-FU), hydroxyurea, etoposide, arabinoside, 6-mercaptopurine, 6-thioguanine, fludarabine, methothexate, steroids, or a combination thereof.
16. The method according to claim 12 , used to treat villous atrophy caused by inflammatory bowel disease (IBD), ulcerative colitis, duodenal ulcers, or Crohn's diseases.
17. A package containing the composition of claim 1 , or powder which, when combined with water, makes a composition of claim 1 , wherein said package further comprises instructions for administering the composition to a patient who has, or who is expected to develop, villous atrophy.
18. The composition, according to claim 1 , which has a total osmolarity from 230 mosm to 280 mosm.
19. The method, according to claim 6 , wherein the composition has a total osmolarity from 230 mosm to 280 mosm.
20. The composition, according to claim 1 , which is sterile.