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 a human subject having dysbiosis of the gastrointestinal microbiota comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat dysbiosis of the gastrointestinal microbiota, 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 an average molecular weight of less than 2000 g/mol.
3. 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.
4. The method of claim 1 , wherein at least 70% of the glycans in the glycan therapeutic preparation have a degree of polymerization (DP) of at least 3 and less than 30 glycan units.
5. 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.
6. 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.
7. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans consisting of one or more of glucose, galactose, arabinose, mannose, fructose, xylose, fucose, or rhamnose glycan units, and the glycan therapeutic preparation has a final solubility limit in water of at least about 70 Brix at 23° C.
8. The method of claim 1 , wherein the treating further comprises administering a second therapeutic agent.
9. The method of claim 1 , wherein the treating further comprises administering a preparation of a probiotic microbe.
10. The method of claim 1 , wherein the treating further comprises administering a polyphenol preparation.
11. The method of claim 1 , wherein the pharmaceutical composition is provided as a unit-dosage form formulated for oral or rectal delivery.
12. The method of claim 1 , wherein the pharmaceutical composition is provided as a unit-dosage form formulated for enteral delivery.
13. The method of claim 1 , wherein administration of the glycan therapeutic modulates the abundance of a bacterial taxa of the microbiota in the subject's gastrointestinal microbiota, thereby treating dysbiosis.
14. The method of claim 1 , wherein administration of the glycan therapeutic modulates the microbial diversity of the microbiota in the subject's gastrointestinal microbiota, thereby treating dysbiosis.
15. The method of claim 1 , wherein the pharmaceutical composition is administered daily.
16. The method of claim 1 , wherein the pharmaceutical composition is administered for a single treatment period.
17. The method of claim 1 , wherein the pharmaceutical composition is administered for more than one treatment period.
18. A method of treating a human subject having dysbiosis of the gastrointestinal microbiota comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat dysbiosis of the gastrointestinal microbiota, 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 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,
iv) at least 60% of the glycans in the glycan therapeutic preparation have an average molecular weight of less than 2000 g/mol,
v) the ratio of alpha- to beta-glycosidic bonds present in the glycans of the glycan therapeutic preparation is between about 1:1 to about 5:1,
vi) 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
vii) the glycan therapeutic preparation has a final solubility limit in water of at least about 70 Brix at 23° C.