MICROBIOME REGULATORS AND RELATED USES THEREOF

• US 20180296582A1
• Filed: 04/23/2016
• Published: 10/18/2018
• Est. Priority Date: 04/23/2015
• Status: Abandoned Application

• Current Assignee: DSM Nutritional Products Incorporated (DSM-Firmenich AG)
• Original Assignee: Kaleido Biosciences Inc
• Inventors: von Maltzahn, Geoffrey A., Geremia, John M.
• Application Number:
  US15/568,251
• Publication Number:
  US 20180296582A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2035/115 Probiotics
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 31/702 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
• CPC Class Codes: A61K 31/716 Glucans
• CPC Class Codes: A61K 31/733 Fructosans, e.g. inulin
• CPC Class Codes: A61K 35/741 Probiotics probiotic yeast, e.g. saccharomyces A61K36/06
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 1/16 : for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C12Q 1/10 : Enterobacteria
• CPC Class Codes: G01N 2800/06 : Gastro-intestinal diseases
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions comprising microbiome regulators are provided, as well as methods of using the same for the modulation of the human microbiota and to treat or prevent related diseases, disorders, or conditions.

Claims

1. A dosage form comprising a composition comprising a microbiome regulator wherein the dosage form targets the release of the composition substantially in one or more of the stomach, small intestine or large intestine, wherein:

i) the microbiome regulator comprises a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol;

ii) the microbiome regulator does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety;

iii) the microbiome regulator comprises a molecule with less than about 12 carbon atoms and less than about 12 heteroatoms, wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus;

or iv) the composition comprises more than about 50% (w/w) of the microbiome regulator.

2. The dosage form of claim 1, wherein the composition is formulated as a unit dosage form.

3. The dosage form of claim 2, wherein the unit dosage form comprises a liquid, a gel, a cream, an ointment, a powder, a tablet, a pill, a capsule, a depository, a single-use applicator, or medical device (e.g. a syringe).

4. The dosage form of any one of claims 2-3, wherein the unit dosage form comprises a liquid dosage form or solid dosage form.

5. The dosage form of any one of claims 2-4, wherein the unit dosage form is formulated for oral administration.

6. The dosage form of claim 4, wherein the unit dosage form is a liquid dosage form formulated for oral administration.

7. The dosage form of claim 6, wherein the liquid dosage form for oral administration comprises a solution, syrup, a suspension, an emulsion, a tincture, or an elixir.

8. The dosage form of claim 4, wherein the unit dosage form is a solid dosage form formulated for oral administration.

9. The dosage form of claim 8, wherein the solid dosage form for oral administration comprises a pill, tablet, or capsule.

10. The dosage form of claim 9, wherein the solid dosage form for oral administration is enterically coated, coated for timed release, or coated for controlled release.

11. The dosage form of any one of claims 2-4, wherein the unit dosage form is formulated for enteral administration.

12. The dosage form of claim 4, wherein the unit dosage form is a liquid dosage form formulated for enteral administration.

13. The dosage form of claim 12, wherein the liquid dosage form for enteral administration comprises a solution, a syrup, a suspension, an emulsion, a tincture, or an elixir.

14. The dosage form of claim 4, wherein the unit dosage form is a solid dosage form formulated for enteral administration.

15. The dosage form of claim 14, wherein the solid dosage form for enteral administration comprises a pill, tablet, capsule, ointment, suppository, or enema.

16. The dosage form of any one of claims 1-15, wherein the dosage form is targeted to the small intestine, e.g., the duodenum, jejunum, or ileum.

17. The dosage form of any one of claims 1-15, wherein the dosage form is targeted to the large intestine, e.g., cecum, colon, or rectum.

18. The dosage form of any one of the preceding claims, wherein the composition comprises at least two microbiome regulators.

19. The dosage form of any one of claims 1-17, wherein the composition comprises at least three microbiome regulators.

20. The dosage form of any one of claims 1-17, wherein the microbiome regulator comprises a sugar or sugar alcohol.

21. The dosage form of claim 20, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

22. A pharmaceutical composition for use in engrafting or improving the colonization of a bacterial taxa in the gastrointestinal microbiota of a subject comprising:

i) a microbiome regulator; and

ii) a bacterial taxa for which either engraftment or an improvement of colonization is sought;

wherein the composition is formulated in a dosage form or dosage regimen to substantially release the microbiome regulator in one or more of the stomach, small intestine or large intestine, wherein the

23. The composition of claim 22, wherein the dosage form is targeted to the small intestine, e.g., the duodenum, jejunum, or ileum.

24. The composition of claim 23, wherein the dosage form is targeted to the large intestine, e.g., cecum, colon, or rectum.

25. The composition of any one of claims 22-25, wherein the microbiome regulator comprises a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol.

26. The composition of any one of claims 22-25, wherein the microbiome regulator comprises a sugar or sugar alcohol.

27. The composition of claim 26, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

28. The composition of any one of claims 22-27, wherein the bacterial taxa is a probiotic.

29. The composition of any one of claims 22-28, wherein the subject does not host the bacterial taxa (e.g., the subject is substantially devoid of the bacterial taxa).

30. The composition of any one of claims 22-29, wherein the microbiome regulator substantially promotes the growth of the bacterial taxa.

31. The composition of claim 28, wherein the probiotic provides a health or treatment effect to the subject.

32. A pharmaceutical composition for use in modulating a bacterial taxa in the gastrointestinal microbiota of a subject comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release of the composition in the gastrointestinal tract of the subject to thereby modulate the bacterial taxa.

33. The composition of claim 32, wherein modulating a bacterial taxa comprises an increase or decrease in the abundance of the taxa.

34. The composition of claim 33, wherein modulating a bacterial taxa comprises an increase or decrease in the abundance of the taxa relative to the abundance of said bacterial taxa in the absence of the composition.

35. The composition of any one of claims 32-34, wherein modulating a bacterial taxa comprises an increase or decrease in the abundance of the taxa relative to the abundance of a second bacterial taxa.

36. The composition of claim 32, wherein the administration of the composition to the subject modulates microbial diversity in the subject.

37. The composition of claim 32, wherein the administration of the composition to the subject modulates a function of the microbiota.

38. The composition of claim 32, wherein modulating a bacterial taxa comprises modulating (e.g., stimulation or downregulation) a metabolic pathway.

39. The composition of claim 38, wherein the modulating a metabolic pathway comprises an increase or decrease in the level of an anti-microbial agent, a secondary bile acid, a short-chain fatty acid, a siderophore, or a metabolite listed in Table 2 by the microbiota.

40. The composition of claim 32, wherein the microbiome regulator comprises a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol.

41. The composition of claim 40, wherein the microbiome regulator comprises a sugar or sugar alcohol.

42. The composition of claim 41, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

43. The composition of claim 41, wherein the sugar or sugar alcohol comprises galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

44. The composition of claim 32, wherein the microbiome regulator comprises a sugar or sugar alcohol that is metabolizable by the host.

45. The composition of claim 32, wherein the microbiome regulator comprises a sugar or sugar alcohol that is non-metabolizable by the host.

46. The composition of claim 41, wherein the composition comprises more than about 50% (w/w) of a sugar or sugar alcohol (e.g., more than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or more).

47. The composition of claim 32, wherein the microbiome regulator comprises a molecule with less than about 12 carbon atoms (e.g., less than about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms) and less than about 12 heteroatoms (e.g., less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms), wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus.

48. The composition of claim 32, wherein the microbiome regulator does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety.

49. The composition of claim 41, wherein the sugar or sugar alcohol has a low degree of sweetness relative to sucrose.

50. The composition of claim 48, wherein the sugar or sugar alcohol has a degree of sweetness less than about 1 relative to sucrose (e.g., less than about 0.95, about 0.9, about 0.85, about 0.8, about 0.75, about 0.7, about 0.65, about 0.6, about 0.55, about 0.5, or less).

51. The composition of claim 48, wherein the sugar or sugar alcohol has a degree of sweetness that less than about 2 relative to sucrose (e.g., less than about 3, about 4, about 5, about 10, about 20, about 25, about 50, about 75, about 100, about 250, about 500, about 1000, or more).

52. The composition of claim 41, wherein the sugar or sugar alcohol has a low absorption coefficient relative to glucose.

53. The composition of claim 51, wherein the sugar or sugar alcohol has a an absorption coefficient less than 0.15 (e.g., less than about 0.14, about 0.13, about 0.12, about 0.11, about 0.10, about 0.09, about 0.08, about 0.07, about 0.06, about 0.05, about 0.04, about 0.03, about 0.02, about 0.01, or less).

54. The composition of claim 44, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the lower GI tract (e.g., the small intestine or large intestine).

55. The composition of claim 54, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the small intestine, e.g., the duodenum, jejunum, or ileum.

56. The composition of claim 54, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the large intestine, e.g., cecum, colon, or rectum.

57. The composition of claim 32, wherein the microbiome regulator comprises an amino acid (e.g., an L-amino acid or a D-amino acid).

58. The composition of claim 32, wherein the microbiome regulator comprises a micronutrient.

59. The composition of claim 58, wherein the micronutrient comprises a vitamin, an element, or a mineral.

60. The composition of claim 32, wherein the microbiome regulator comprises a fatty acid.

61. The composition of claim 60, wherein the fatty acid comprises a short-chain fatty acid (SCFA), a medium-chain fatty acid (MCFA), a long-chain fatty acid (LCFA), or a very long chain fatty acid (VLCFA).

62. The composition of claim 32, wherein the microbiome regulator comprises a polyphenol.

63. The composition of claim 62, wherein the polyphenol comprises a catechin, ellagitannin, isoflavone, flavonol, flavanone, anthocyanin, or lignin.

64. A pharmaceutical composition for use in treating a subject having a dysbiosis of the gastrointestinal microbiota comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release of the composition in the gastrointestinal tract to thereby treat the subject.

65. The composition of claim 64, wherein the dysbiosis is idiopathic (e.g., the subject has no substantially observable cause of a dysbiosis).

66. The composition of claim 64, wherein the dysbiosis is associated with a disease, disorder, or condition in the subject.

67. The composition of claim 66, wherein the disease, disorder, or condition comprises an infectious disease, an inflammatory disease, a metabolic disease, an autoimmune disease, a neurological disease, or a cancer.

68. The composition of claim 67, wherein infectious disease comprises Clostridium difficile infection (CDI);

Vancomycin-resistant enterococci (VRE) infection, infectious colitis, C. difficile colitis, a mycosis (e.g., Candida albicans infection, Campylobacter jejuni infection, or Helicobacter pylori infection), Clostridium difficile associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), antibiotic-induced diarrhea, travelers'"'"' diarrhea (TD), pediatric diarrhea, or (acute) infectious diarrhea.

69. The composition of claim 67, wherein the inflammatory disease comprises inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn'"'"'s disease (CD), idiopathic inflammation of the small bowel, indeterminatal colitis, pouchitis, irritable bowel syndrome (IBS), necrotizing enterocolitis (NEC), intestinal inflammation, constipation, microscopic colitis, diarrhea, graft versus host disease (GVHD), allergies (e.g., food allergies), pseudomembranous colitis, indigestion, non-ulcer dyspepsia, diverticulosis, diverticulitis, ischemic colitis, radiation colitis, radiation enteritis, collagenous colitis, gastroenteritis, or polyps.

70. The composition of claim 67, wherein the metabolic disease comprises obesity, (insulin resistance) pre-diabetes, type II diabetes, high fasting blood sugar (hyperglycemia), metabolic syndrome, or a cardiovascular risk factor (e.g., high blood cholesterol, high LDL, high blood pressure (hypertension), high triglyceride levels, low HDL).

71. The composition of claim 67, wherein the autoimmune disease comprises autoimmune arthritis, type I diabetes, multiple sclerosis, psoriasis, an allergy, asthma, or atopic dermatitis.

72. The composition of claim 67, wherein the neurological disease comprises autism, hyperammonemia, or hepatic encephalopathy.

73. The composition of claim 67, wherein the cancer comprises a cancer of the brain, skin, blood, bone, eye, breast, lung, prostate, liver, or gastrointestinal tract.

74. The composition of claim 64, wherein the dysbiosis is associated with a gastrointestinal disease.

75. The composition of claim 64, wherein the microbiome regulator is a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol.

76. The composition of claim 75, wherein the microbiome regulator comprises a sugar or sugar alcohol.

77. The composition of claim 76, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

78. The composition of claim 76, wherein the sugar or sugar alcohol comprises galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

79. The composition of claim 76, wherein the microbiome regulator comprises a sugar or sugar alcohol that is metabolizable by the host.

80. The composition of claim 76, wherein the microbiome regulator comprises a sugar or sugar alcohol that is non-metabolizable by the host.

81. The composition of claim 64, wherein the composition comprises more than about 50% (w/w) of a sugar or sugar alcohol (e.g., more than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or more).

82. The composition of claim 64, wherein the microbiome regulator comprises a molecule with less than about 12 carbon atoms (e.g., less than about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms) and less than about 12 heteroatoms (e.g., less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms), wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus.

83. The composition of claim 64, wherein the microbiome regulator does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety.

84. The composition of claim 76, wherein the sugar or sugar alcohol has a low degree of sweetness relative to sucrose.

85. The composition of claim 84, wherein the sugar or sugar alcohol has a degree of sweetness less than about 1 relative to sucrose (e.g., less than about 0.95, about 0.9, about 0.85, about 0.8, about 0.75, about 0.7, about 0.65, about 0.6, about 0.55, about 0.5, or less).

86. The composition of claim 84, wherein the sugar or sugar alcohol has a degree of sweetness less than about 2 relative to sucrose (e.g., less than about 3, about 4, about 5, about 10, about 20, about 25, about 50, about 75, about 100, about 250, about 500, about 1000, or more).

87. The composition of claim 76, wherein the sugar or sugar alcohol has a low absorption coefficient relative to glucose.

88. The composition of claim 87, wherein the sugar or sugar alcohol has a an absorption coefficient less than 0.15 (e.g., less than about 0.14, about 0.13, about 0.12, about 0.11, about 0.10, about 0.09, about 0.08, about 0.07, about 0.06, about 0.05, about 0.04, about 0.03, about 0.02, about 0.01, or less).

89. The composition of claim 78, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the lower GI tract (e.g., the small intestine or large intestine).

90. The composition of claim 88, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the small intestine, e.g., the duodenum, jejunum, or ileum.

91. The composition of claim 88, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the large intestine, e.g., cecum, colon, or rectum.

92. The composition of claim 64, wherein the microbiome regulator comprises an amino acid.

93. The composition of claim 64, wherein the microbiome regulator comprises a micronutrient (e.g., a vitamin, an element, or a mineral).

94. The composition of claim 64, wherein the microbiome regulator comprises a fatty acid.

95. The composition of claim 94, wherein the fatty acid comprises a short-chain fatty acid (SCFA), a medium-chain fatty acid (MCFA), a long-chain fatty acid (LCFA), or a very long chain fatty acid (VLCFA).

96. The composition of claim 64, wherein the microbiome regulator comprises a polyphenol.

97. The composition of claim 96, wherein the polyphenol comprises a catechin, ellagitannin, isoflavone, flavonol, flavanone, anthocyanin, or lignin.

98. A pharmaceutical composition for use in reducing a drug- or treatment-induced symptom in a subject comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release of the composition in the gastrointestinal tract to thereby reduce the symptom in the subject.

99. The composition of claim 98, wherein the composition comprises one or more of:

i) a microbiome regulator comprising a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol;

ii) a microbiome regulator that does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety;

iii) a microbiome regulator comprising a molecule with less than about 12 carbon atoms (e.g., less than about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms) and less than about 12 heteroatoms (e.g., less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms), wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus;

and iv) a composition comprising more than about 50% (w/w) of a microbiome regulator (e.g., more than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or more).

100. The composition of any one of claims 98-99, wherein the drug- or treatment-induced symptom is bloating, diarrhea, vomiting, nausea, and constipation.

101. The composition of claim 100, wherein the drug- or treatment-induced is diarrhea.

102. The composition of claim 100, wherein the drug- or treatment-induced symptom is constipation.

103. The composition of claim 98, wherein the composition is administered prior to, concomitant with, or after administration of the drug.

104. The composition of claim 99, wherein the composition comprises at least two of i), ii), iii), or iv).

105. The composition of claim 99, wherein the composition comprises at least three of i), ii), iii), or iv).

106. The composition of claim 99, wherein the composition consists of i), ii), iii), and iv).

107. The composition of claim 99, wherein the microbiome regulator comprises a sugar or sugar alcohol.

108. The composition of claim 107, wherein the microbiome regulator comprises a sugar or sugar alcohol that is metabolizable by the host.

109. The composition of claim 107, wherein the microbiome regulator comprises a sugar or sugar alcohol that is non-metabolizable by the host.

110. The composition of claim 108, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the lower GI tract (e.g., the small intestine or large intestine).

111. The composition of claim 110, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the small intestine, e.g., the duodenum, jejunum, or ileum.

112. The composition of claim 110, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the large intestine, e.g., cecum, colon, or rectum.

113. A pharmaceutical composition for use in treating a subject having a disease, disorder, or condition requiring control of the blood sugar level (e.g., blood glucose level) of the subject, and wherein the subject would benefit from treatment with a composition comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release in the lower gastrointestinal tract (e.g., the small intestine or large intestine), thereby substantially limiting systemic exposure to the microbiome regulator.

114. The composition of claim 113, wherein the microbiome regulator comprises a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol.

115. The composition of claim 113, wherein the microbiome regulator comprises a sugar or sugar alcohol.

116. The composition of claim 113, wherein the microbiome regulator comprises a sugar or sugar alcohol that is metabolizable by the host.

117. The composition of claim 113, wherein the microbiome regulator comprises a sugar or sugar alcohol that is non-metabolizable by the host.

118. The composition of claim 115, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

119. The composition of claim 115, wherein the sugar or sugar alcohol comprises glucose.

120. The composition of claim 113, wherein the disease, disorder, or condition comprises cancer.

121. The composition of claim 113, wherein the disease, disorder, or condition is a metabolic disease.

122. The composition of claim 121, wherein the metabolic disease, disorder, or condition comprises diabetes.

123. The composition of claim 113, wherein the benefiting from treatment with a composition comprising a microbiome regulator comprises one or more of:

i) treating a dysbiosis in the subject;

ii) treating a reducing a drug- or treatment-induced symptom in the subject;

or

iii) modulating a bacterial taxa in the gastrointestinal microbiota of the subject to provide a health benefit to the subject.

124. The composition of claim 123, wherein the composition comprises at least two of i), ii), or iii).

125. The composition of claim 123, wherein the composition consists of i), ii), and iii).

126. The composition of claim 113, wherein the microbiome regulator does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety.

127. The composition of claim 113, wherein the microbiome regulator comprises a molecule with less than about 12 carbon atoms (e.g., less than about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms) and less than about 12 heteroatoms (e.g., less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms), wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus.

128. The composition of claim 113, wherein the composition comprises more than about 50% (w/w) of a microbiome regulator (e.g., more than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or more).

129. The composition of claim 113, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the small intestine, e.g., the duodenum, jejunum, or ileum.

130. The composition of claim 113, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the large intestine, e.g., cecum, colon, or rectum.

131. The composition of claim 113, wherein the composition is a liquid dosage form or solid dosage form formulated for oral or enteral administration.

132. A pharmaceutical composition for use in modulating microbial diversity in the gastrointestinal microbiota of a subject comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release of the composition in the gastrointestinal tract to thereby modulate microbial diversity in the subject.

133. The composition of claim 132, wherein the microbial diversity comprises bacterial diversity.

134. The composition of claim 132, wherein the Shannon diversity of the microbiota is increased or decreased by at least about 5% (e.g., at least about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or more).

135. The composition of claim 132, wherein the Shannon diversity of the microbiota is increased or decreased by at least about 0.1 log-fold (e.g., about 0.2 log-fold, about 0.3 log-fold, about 0.4 log-fold, about 0.5 log-fold, about 0.6 log-fold, about 0.7-log-fold, about 0.8 log-fold, about 0.9 log-fold, about 1 log-fold, about 1.5 log-fold about 2 log-fold, or more).

136. A pharmaceutical composition for use in treating a subject having a gastrointestinal disease comprising a microbiome regulator formulated in a dosage form or administered in a dosage regimen for substantial release of the composition in the gastrointestinal tract of the subject, provided that if the microbiome regulator comprises glucose, the microbiome regulator is provided in a dosage form that is enterically coated.

137. The composition of claim 136, wherein the microbiome regulator is a sugar or sugar alcohol comprising one or more of:

i) a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, or pentasaccharide that is metabolized by the host;

wherein if the sugar or sugar alcohol is a disaccharide, trisaccharide, tetrasaccharide, or pentasaccharide;

a) at least one, at least two, at least three, at least four, or more glycosidic bonds comprise a 1->

2 glycosidic bond, a 1->

3 glycosidic bond, a 1->

4 glycosidic bond, or a 1->

6 glycosidic bond; and

b) at least one, at least two, at least three, at least four, or more of the glycosidic bonds are present in the alpha or beta configuration;

ii) a molecular weight less than about 1000 g/mol (e.g., less than about 950 g/mol, about 900 g/mol, about 850 g/mol, about 800 g/mol, about 750 g/mol, about 700 g/mol, about 650 g/mol, about 600 g/mol, about 500 g/mol, about 450 g/mol, about 400 g/mol, about 350 g/mol, about 300 g/mol, about 250 g/mol, about 200 g/mol, or less);

iii) less than about 30 carbon atoms (e.g., less than about 25 carbon atoms, about 20 carbon atoms, about 18 carbon atoms, about 15 carbon atoms, about 12 carbon atoms, about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms);

iv) less than about 30 heteroatoms (e.g., less than about 25 heteroatoms, about 20 heteroatoms, about 18 heteroatoms, less than about 15 heteroatoms, less than about 12 heteroatoms, less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms);

or

v) does not comprise an alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, halogen, acyl, thiol, cyano, nitro, or sulfonyl moiety.

138. The composition of claim 137, wherein the composition comprises at least two of i), ii), iii), iv), or v).

139. The composition of claim 137, wherein the composition comprises at least three of i), ii), iii), iv), or v).

140. The composition of claim 137, wherein the composition comprises at least four of i), ii), iii), iv), or v).

141. The composition of claim 137, wherein the composition consists of i), ii), iii), iv), and v).

142. The composition of claim 136, wherein the composition comprises a sugar or sugar alcohol and one or more of the following:

i) is substantially free of a sugar or sugar alcohol that is not metabolized by the host; and

ii) is substantially free of an agent other than a microbiome regulator, e.g., a therapeutic agent (e.g., peptide, nucleic acid, oligosaccharide, polysaccharide, protein, non-peptide small molecule, or a prodrug or metabolite thereof), or

a polymer (e.g. is polyethylene glycol (PEG), polypropylene glycol (PPG), polyvinyl pyrrolidine (PVG), polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyacrylamide, N-(2-hydroxypropyl) methylacrylamide (HMPA), divinyl ether-maleic anhydride (DIVEMA), polyoxazolines, polyphosphates, xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, cellulose (e.g., hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethylcellulose (HEC), sodium carboxymethyl cellulose (NaCMC)), hyaluronic acid, hyaluronan, albumin, heparin, chondroitin, starch, or derivatives thereof).

143. The composition of claim 142, wherein the composition consists of i) and ii).

144. The composition of claim 142, wherein the agent other than a microbiome regulator is a therapeutic agent and comprises one or more of:

i) a peptide, nucleic acid, oligosaccharide, polysaccharide, protein, non-peptide small molecule, or a prodrug or metabolite thereof;

ii) a molecular weight greater than about 500 g/mol;

iii) more than about 6 carbon atoms;

iv) a specificity for a cell surface receptor, an ion channel, a transporter, an enzyme, an antibody, or other biological target;

or

v) an agent used in the treatment of a disease, disorder, or condition.

145. The composition of claim 144, wherein the composition comprises at least two of i), ii), iii), iv), or v).

146. The composition of claim 144, wherein the composition comprises at least three of i), ii), iii), iv), or v).

147. The composition of claim 144, wherein the composition comprises at least four of i), ii), iii), iv), or v).

148. The composition of claim 145, wherein the composition consists of i), ii), iii), iv), and v).

149. The composition of claim 136, further comprising identifying a subject in need of treatment of a gastrointestinal disease.

150. The composition of claim 149, wherein the subject in need of treatment of a gastrointestinal disease is identified based on assessing of the state of the microbiota of the subject.

151. The composition of claim 150, wherein the assessing comprises acquiring (e.g., directly or indirectly) knowledge of either the specific OTU or the microbial diversity of the gastrointestinal microbiota of the subject.

152. The composition of claim 149, wherein the identifying comprises acquiring (e.g., directly or indirectly) a sample from the subject (e.g., a fecal sample).

153. The composition of any one of claim 150 or 152, wherein an effective amount of a composition comprising a microbiome regulator is administered based on the results of the assessing.

154. The composition of claim 136, further comprising identifying a subject having a dysbiosis.

155. A pharmaceutical composition comprising a microbiome regulator comprising a sugar, a sugar alcohol, an amino acid, a peptide, a micronutrient, a fatty acid, or a polyphenol, formulated in a dosage form or administered in a dosage regimen that targets the release of the composition substantially to the gastrointestinal tract.

156. The composition of claim 155, wherein the microbiome regulator comprises a sugar or sugar alcohol.

157. The composition of claim 155, wherein the sugar or sugar alcohol comprises glucose, galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

158. The composition of claim 155, wherein the sugar or sugar alcohol comprises galactose, fructose, fucose, mannose, xylose, arabinose, rhamnose, ribose, sucrose, sorbose, lactose, sorbitol, maltose, mannitol, lactulose, lactitol, erythritol, tagatose, kojibiose, nigerose, isomaltose, trehalose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiulose, mannobiose, melibiulose, rutinulose, or xylobiose.

159. The composition of claim 156, wherein the microbiome regulator comprises a sugar or sugar alcohol that is metabolizable by the host.

160. The composition of claim 156, wherein the microbiome regulator comprises a sugar or sugar alcohol that is non-metabolizable by the host.

161. The composition of claim 155, wherein the composition comprises more than about 50% (w/w) of a sugar or sugar alcohol (e.g., more than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or more).

162. The composition of claim 155, wherein the microbiome regulator comprises a molecule with less than about 12 carbon atoms (e.g., less than about 10 carbon atoms, about 9 carbon atoms, about 8 carbon atoms, about 7 carbon atoms, about 6 carbon atoms, or about 5 carbon atoms) and less than about 12 heteroatoms (e.g., less than about 10 heteroatoms, less than about 9 heteroatoms, less than about 8 heteroatoms, less than about 7 heteroatoms, less than about 6 heteroatoms, or less than about 5 heteroatoms), wherein the heteroatom is selected from oxygen, nitrogen, sulfur, or phosphorus.

163. The composition of claim 159, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the lower GI tract (e.g., the small intestine or large intestine).

164. The composition of claim 163, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the small intestine, e.g., the duodenum, jejunum, or ileum.

165. The composition of claim 163, wherein a substantial portion of the sugar or sugar alcohol that is metabolized by the host is metabolized in the large intestine, e.g., cecum, colon, or rectum.

166. The composition of claim 155, wherein the microbiome regulator comprises an amino acid.

167. The composition of claim 155, wherein the microbiome regulator comprises a micronutrient.

168. The composition of claim 167, wherein the micronutrient comprises a vitamin, an element, or a mineral.

169. The composition of claim 155, wherein the microbiome regulator comprises a fatty acid.

170. The composition of claim 169, wherein the fatty acid comprises a short-chain fatty acid (SCFA), a medium-chain fatty acid (MCFA), a long-chain fatty acid (LCFA), or a very long chain fatty acid (VLCFA).

171. The composition of claim 155, wherein the microbiome regulator comprises a polyphenol.

172. The composition of claim 171, wherein the polyphenol comprises a catechin, ellagitannin, isoflavone, flavonol, flavanone, anthocyanin, or lignin.