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 gycan therapeutics, e.g. for the modulation of human gastrointestinal microbiota and to treat dysbioses.
1. A method of treating a human subject colonized or being at risk of being colonized by a pathogen in the gastrointestinal tract comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat the pathogen colonization, 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 70% of the glycans in the glycan therapeutic preparation have an average molecular weight of less than 1900 g/mol.
3. 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.
4. The method of claim 1 , wherein the average degree of polymerization of the glycan therapeutic preparation is between about DP6 and about DP10.
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, gastric, or rectal delivery.
12. The method of claim 1 , wherein the subject is asymptomatic.
13. The method of claim 1 , wherein the subject has a bacterial infection.
14. The method of claim 13 , wherein the bacterial infection comprises diarrhea, fever, chills, urinary tract infection (UTI), bacteremia, endocarditis, intra-abdominal infection, pelvic infection, or respiratory infection.
15. The method of claim 1 , wherein the subject is hospitalized, a resident in a long-term care facility, a health care worker, a long-term antibiotics user, immunosuppressed, connected to an indwelling device, or undergoes surgery.
16. The method of claim 1 , wherein the pathogen is an Enterococcus or an Enterobacteriaceae.
17. The method of claim 16 , wherein the pathogen is antibiotic-resistant.
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.