Glycan therapeutics and method of treating conditions associated with TMAO
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 having a disease or disorder associated with elevated levels of trimethylamine N-oxide (TMAO) comprising administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to treat the disease or disorder, 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 the disease or disorder associated with elevated levels of TMAO is chronic kidney disease (CKD).
3. The method of claim 1 , wherein the average DP of the glycan therapeutic preparation is between about DP6 and about DP12.
4. The method of claim 1 , wherein at least 60% of the glycan therapeutic preparation has an average molecular weight of less than 2000 g/mol.
5. The method of claim 1 , wherein the average degree of branching (DB) of the branched glycans in the glycan therapeutic preparation is between 0.05 and 0.25.
6. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans consisting of glucose glycan units.
7. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans consisting of glucose and mannose glycan units.
8. The method of claim 1 , wherein the pharmaceutical composition is administered daily.
9. The method of claim 1 , wherein the method further comprises administering a second drug or pharmaceutical composition.
10. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans comprising glucose glycan units.
11. The method of claim 1 , wherein the glycan therapeutic preparation comprises branched glycans comprising glucose and mannose glycan units.