Prevention or Treatment of Immune-Relevant Disease by Modification of Microfloral Populations

• US 20110086011A1
• Filed: 06/03/2009
• Published: 04/14/2011
• Est. Priority Date: 06/04/2008
• Status: Active Grant

• Current Assignee: The Trustees of Dartmounth College (Dartmouth College)
• Original Assignee: The Trustees of Dartmounth College (Dartmouth College)
• Inventors: Ochoa-Repáraz, Javier, Kasper, Lloyd H.
• Granted Patent: US 8,586,029 B2
• Time in Patent Office: Days
• US Class Current: 424/93.41
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/744 Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• CPC Class Codes: A61K 35/745 Bifidobacteria
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 36/064 Saccharomycetales, e.g. baker's yeast
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention is a method for preventing or treating an immune-relevant disease by modulating commensal microbiota populations via antibiotics, exogenous microbiota and/or probiotics.

Claims

1. A method for preventing or treating an immune-relevant disease comprising administering to a subject in need of treatment an effective amount of one or more antibiotics to modulate commensal microbiota populations and subsequently administering exogenous microflora that express capsular polysaccharide thereby preventing or treating an immune-relevant disease in the subject.

3. The method of claim 1, wherein the antibiotic comprises ampicillin, vancomycin, neomycin sulfate, metronidazole, Amoxicillin, Alatrofloxacin, Tetracycline, Moxifloxacin, Azithromycin, Bacampicillin, Oxacillin, Benzylpenicillin, Clarithromycin, Carbenicillin, Cefadroxil, Cephalexin, Cefditoren, Cefepime, Cefmetazole, Cefoperazone, Cefprozil, Cephalexin, Clarithromycin, Clindamycin, Daptomycin, Dicloxacillin, Erythromycin, Gemifloxacin, Sulfamethoxazole, Kanamycin, Levofloxacin, Lincomycin, Lomefloxacin, Vancomycin, Meropenem, Nafcillin, Nalidixic Acid, Tobramycin, Piperacillin, Polymyxin, Trimethoprim, Rifampin, Streptomycin, Trovafloxacin, Vancomycin, or combinations thereof.

4. The method of claim 1, wherein the antibiotic is a combination of ampicillin, vancomycin, neomycin sulfate, and metronidazole.

5. The method of claim 1, wherein the antibiotic is administered orally.

7. The method of claim 1, wherein the exogenous microflora is commensal.

8. The method of claim 1, wherein the microflora is from the genus Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, Bifidobacterium, Escherichia, or Lactobacillus.

9. The method of claim 1, wherein the microflora is Bacteroides ovatus, B. thetaiotaomicron, B. fragilis, or B. intestinalis.

10. The method of claim 1, wherein the capsular polysaccharide is PSA, PSB, PSC, PSD, PSE, PSF, PSG, or PSH.

11. The method of claim 1, further comprising administering one or more probiotics.

12. The method of claim 11, wherein the probiotic comprises Lactobacillus acidophilus or Saccharomyces boulardii.

13. The method of claim 1, wherein the immune-relevant disease comprises multiple sclerosis, Crohn'"'"'s disease, rheumatoid arthritis, cancer or HIV.

14. The method of claim 1, wherein the immune-relevant disease is multiple sclerosis.

2. (canceled)

6. (canceled)

15. A method for transferring protection to an immune-relevant disease comprising isolating regulatory T cells from a first subject colonized with a Bacteroides and administering said regulatory T cells to a second subject having an immune-relevant disease so that protection to the immune-relevant disease is transferred from the first subject to the second subject.

16. The method of claim 15, wherein the Bacteroides is Bacteroides ovatus, B. thetaiotaomicron, B. fragilis, or B. intestinalis.

17. The method of claim 15, wherein the immune-relevant disease is multiple sclerosis.