METHOD FOR TREATMENT OF DISORDERS OF THE GASTROINTESTINAL SYSTEM

• US 20140363397A1
• Filed: 09/14/2012
• Published: 12/11/2014
• Est. Priority Date: 09/14/2011
• Status: Abandoned Application

• Current Assignee: Kingston Health Sciences Centre, Queen's University At Kingston, University of Guelph
• Original Assignee: Kingston General Hospital, Queen's University At Kingston, University of Guelph
• Inventors: Allen-Vercoe, Emma, Petrof, Elaine Olga
• Application Number:
  US14/344,981
• Publication Number:
  US 20140363397A1
• Time in Patent Office: Days
• US Class Current: 424/93.3
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/745 Bifidobacteria
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• 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 31/04 Antibacterial agents
• CPC Class Codes: C12N 1/20 Bacteria; Culture media therefor
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12R 2001/01 Bacteria or Actinomycetales ; using bacteria or Actinomycetales
• CPC Class Codes: C12R 2001/145 Clostridium

Abstract

There are provided novel synthetic stool preparations comprising bacteria isolated from a fecal sample from a healthy donor. The synthetic stool preparations are used for treating disorders of the gastrointestinal tract, including dysbiosis, Clostridium difficile infection and recurrent Clostridium difficile infection, prevention of recurrence of Clostridium difficile infection, treatment of Crohn'"'"'s disease, ulcerative colitis, irritable bowel syndrome, inflammatory bowel disease, and diverticular disease, and treatment of food poisoning such as salmonella. Methods of preparation and methods of use of the synthetic stool preparations are also provided.

Claims

1. A synthetic stool preparation comprising a mixture of bacterial strains, wherein at least one of the bacterial strains is selected from the strains listed in Table 1 or Table 7, or from strains having all of the identifying characteristics of the strains listed in Table 1 or Table 7.

2. The synthetic stool preparation of claim 1, wherein the mixture comprises two or more, ten or more, 15 or more, 20 or more, 25 or more or 30 or more bacterial strains selected from the strains listed in Table 1 or Table 7, or two or more, ten or more, 15 or more, 20 or more, 25 or more or 30 or more strains having all of the identifying characteristics of two or more corresponding strains listed in Table 1 or Table 7.

5. The synthetic stool preparation of claim 1, wherein the mixture comprises at least one bacterial strain selected from the strains listed in Table 2a or Table 9, or from strains having all of the identifying characteristics of the strains listed in Table 2a or Table 9.

6. The synthetic stool preparation of claim 1, wherein the mixture comprises ten or more, 15 or more, 20 or more, 25 or more or 30 or more bacterial strains selected from the strains listed in Table 2a or Table 9, or ten or more, 15 or more, 20 or more, 25 or more or 30 or more strains having all of the identifying characteristics of ten or more corresponding strains listed in Table 2a or Table 9.

10. The synthetic stool preparation of claim 1, wherein the mixture comprises:

at least one bacterial strain which produces butyrate, at least one Bacteroides spp. strain, at least one Clostridium cluster XIVa group bacterial strain, at least one Bifidobacterium longum bacterial strain, or at least one Lachnospiraceae bacterial strain.

15. The synthetic stool preparation of claim 1, wherein the mixture comprises more than one strain of at least one single bacterial species.

16. The synthetic stool preparation of claim 1, wherein the mixture comprises at least one bacterial strain selected from the group consisting of strain 13LG (Eubacterium limosum), strain 31 FAA (Roseburia intestinalis), F. prausnitzii, Roseburia spp., Eubacterium rectale, B. ovatus, P. distasonis, Eubacterium eligens, Eubacterium ventriosum, Roseburia spp., Blautia spp., Dorea spp., R. torques, Bifidobacterium longum, Eubacterium hadrum, Anaerostipes coli, Clostridium spp. aldenense, Clostridium spp. (hathewayi, symbiosum, orbiscindens, thermocellum, citroniae), Ruminococcus obeum, Ruminococcus productus, Ruminococcus torques, Ruminococcus bromii, Roseburia inulinovorans, Blautia coccoides, Dorea spp., Sutterella spp., Dialister invisus, Blautia producta, Bifidobacterium pseudocatenulatum, and strains having the identifying characteristics thereof.

20. The synthetic stool preparation of claim 1, wherein at least one of the bacterial strains in the mixture is antagonistic towards Clostridium difficile, inhibits or prevents sporulation of Clostridium difficile, or neutralizes or protects against Clostridium difficile toxin.

21. The synthetic stool preparation of claim 20, wherein the at least one bacterial strain which inhibits or prevents sporulation of Clostridium difficile is Roseburia intestinalis strain 31 FAA, or a strain having all of the identifying characteristics thereof.

23. The synthetic stool preparation of claim 1, wherein the synthetic stool preparation further comprises insoluble fiber, a buffer, an osmotic agent, an anti-foaming agent, and/or a preservative.

26. The synthetic stool preparation of claim 1, wherein the synthetic stool preparation is made or provided under reduced atmosphere, wherein the preparation is under N₂, CO₂, H₂, or a mixture thereof.

29. A method for treating a disorder associated with dysbiosis of the gastrointestinal tract, comprising administering the synthetic stool preparation of claim 1 to a subject in need thereof.

30. The method of claim 29, wherein administration is via rectal enema by the colonoscopic route.

31. The method of claim 30, comprising the steps of:

inserting a colonoscope into the cecum of the subject;

optionally suctioning a sample of fecal material from the area;

depositing a first portion of the synthetic stool preparation adjacent to the cecum, using a syringe containing the synthetic stool preparation attached to the colonoscope; and

depositing a second portion of the synthetic stool preparation throughout the transverse colon using the syringe as the colonoscope is withdrawn.

32. The method of claim 29, wherein the subject does not receive antibiotic therapy for at least 3 days before administration of the synthetic stool preparation.

33. The method of claim 29, wherein the subject is treated with a colon cleansing agent before administration of the synthetic stool preparation.

35. The method of claim 29, wherein the subject has Clostridium difficile infection or recurrent Clostridium difficile infection, or wherein recurrence of Clostridium difficile infection is prevented.

39. The method of claim 29, wherein the subject has Crohn'"'"'s disease, ulcerative colitis, irritable bowel syndrome, inflammatory bowel disease, diverticular disease, or food poisoning.

65. A method for preparing the synthetic stool preparation of claim 1, wherein the bacterial strains are cultured in a chemostat containing chemostat medium, under reduced atmosphere with controlled levels of partial pressure of N₂:

CO₂;

H₂, and controlled acidity (pH) to replicate human colonic gastrointestinal tract in equilibrium;

individual bacterial strains are then purified into pure isolates; and

the pure isolates are combined to produce the synthetic stool preparation.

67. The method of claim 65, wherein the combined isolates are grown in a single-stage chemostat system.

68. The method of claim 67, wherein the combined isolates are grown in batch culture, or the combined isolates are grown in batch culture after growth in the single-stage chemostat system.

72. The method of claim 29, wherein inflammation is reduced in the subject after administration of the synthetic stool preparation.

73. The method of claim 29, wherein the synthetic stool preparation is administered orally.

74. The method of claim 73, wherein the synthetic stool preparation is freeze-dried and/or is in capsule or tablet form.

3. (canceled)

4. (canceled)

7. (canceled)

8. A synthetic stool preparation comprising a mixture of bacterial strains, wherein the mixture comprises some or all of the bacterial strains listed in Table 2a or Table 9.

9. (canceled)

11-14. -14. (canceled)

17-19. -19. (canceled)

22. (canceled)

24. (canceled)

25. (canceled)

27. (canceled)

28. (canceled)

34. (canceled)

36-38. -38. (canceled)

40-64. -64. (canceled)

66. (canceled)

69-71. -71. (canceled)

75-79. -79. (canceled)