Glycan therapeutics and related methods thereof
Preparations of glycan therapeutics, pharmaceutical compositions and medical foods thereof, optionally comprising micronutrients, polyphenols, prebiotics, probiotics, or other agents are provided and methods of making same. Also provided are methods of using said glycan therapeutics, e.g. for the modulation of human gastrointestinal microbiota and to treat dysbioses.
1. A method of treating an obese human subject comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat obesity, wherein:
i) the glycan therapeutic preparation comprises branched glycans that comprise glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units,
ii) the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is between 0.01 and 0.5,
iii) at least 50% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units,
iv) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 0.8:1 to about 5:1,
v) at least two of the glycosidic bonds independently comprise a 1→2 glycosidic bond, a 1→3 glycosidic bond, a 1→4 glycosidic bond, or a 1→6 glycosidic bond, and
vi) the glycan therapeutic preparation has a final solubility limit in water of at least about 60 Brix at 23° C.
2. The method of claim 1 , wherein at least 60% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units.
3. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans that comprise at least two of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units.
4. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans that comprise at least three of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units.
5. The method of claim 1 , wherein the glycan therapeutic preparation comprises at least three glycosidic bonds that independently comprise a 1→2 glycosidic bond, a 1→3 glycosidic bond, a 1-4 glycosidic bond, or a 1→6 glycosidic bond.
6. The method of claim 1 , wherein the treating further comprises administering a second therapeutic agent.
7. The method of claim 1 , wherein the treating further comprises administering a preparation of a probiotic microbe.
8. The method of claim 1 , wherein the treating further comprises administering a polyphenol preparation.
9. The method of claim 1 , wherein the pharmaceutical composition is provided as a unit-dosage form formulated for oral or rectal delivery.
10. The method of claim 1 , wherein the pharmaceutical composition is provided as a unit-dosage form formulated for enteral delivery.
11. The method of claim 1 , wherein treatment comprises decreasing body weight.
12. The method of claim 1 , wherein treatment comprises decreasing body fat.
13. The method of claim 1 , wherein the subject further exhibits metabolic syndrome.
14. The method of claim 13 , wherein the metabolic syndrome comprises elevated blood pressure, elevated fasting plasma glucose, elevated serum triglycerides, or low high-density lipoprotein (HDL) levels.
15. The method of claim 1 further comprising diagnosing body weight, fasting lipid levels, liver function, glucose levels, insulin levels, glycosylated hemoglobin (HbAlC), or glucose tolerance.
16. The method of claim 1 , wherein the subject exhibits or is at risk of developing diabetes, high blood pressure, heart disease, stroke, high cholesterol, sleep apnea, or arthritis.
17. The method of claim 1 , wherein treatment further comprises diet and exercise.
18. The method of claim 1 , wherein the pharmaceutical composition is administered daily.
19. The method of claim 1 , wherein the pharmaceutical composition is administered for a single treatment period.
20. The method of claim 1 , wherein the pharmaceutical composition is administered for more than one treatment period.