Glycan therapeutics for reducing blood ammonia
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 reducing blood ammonia levels in a human subject comprising: administering to the subject a pharmaceutical composition comprising a glycan therapeutic preparation in an amount effective to reduce serum ammonia levels, 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 subject has liver damage.
3. The method of claim 2 , wherein the liver damage comprises liver inflammation, fibrosis, or cirrhosis.
4. The method of claim 1 , wherein the subject has or is at risk of developing non-alcoholic fatty liver disease (NAFLD).
5. The method of claim 4 , wherein the NAFLD is asymptomatic.
6. The method of claim 4 , wherein the NAFLD progresses or has progressed to nonalcoholic steatohepatitis (NASH).
7. The method of claim 1 , wherein the subject has hyperammonemia.
8. The method of claim 1 , wherein reducing the blood ammonia levels in a human subject at risk of hepatic encephalopathy (HE) decreases the occurrence of an initial episode of HE.
9. The method of claim 1 , wherein reducing the blood ammonia levels in a human subject having HE decreases the incidence of future episodes of HE.
10. The method of claim 1 , wherein the subject is asymptomatic.
11. The method of claim 1 , wherein the subject is suspected of developing or at risk of developing HE.
12. The method of claim 1 , wherein the subject has or has been diagnosed with HE.
13. The method of claim 12 , wherein the subject has overt HE.
14. The method of claim 13 , wherein the HE is mild HE or severe HE.
15. The method of claim 1 , wherein reduction in blood ammonia levels reduces one or more neurological symptoms.
16. The method of claim 15 , wherein symptoms are one or more of: confusion, forgetfulness, anxiety or excitation, sudden changes in personality or behavior, changes in sleep patterns, disorientation, sweet or musty smelling breath, slurred speech, and/or difficulty controlling motor functions.
17. The method of claim 16 , wherein the symptoms are decreased by an average of about 10%, about 30%, about 60%, or about 90% when compared to symptoms prior to the administration of a pharmaceutical glycan therapeutic composition.
18. The method of claim 1 , wherein the glycan therapeutic preparation is administered to the subject prior to, concomitant with, or after administration of an antibiotic.
19. The method of claim 1 , wherein the glycan therapeutic preparation is administered to the subject prior to, concomitant with, or after administration of lactulose or lactitol.
20. The method of claim 1 , wherein blood ammonia levels are decreased by 5%, 10%, 20%, 30%, 50% compared to a control.