METHODS OF TREATING AUTOIMMUNE DISEASES CAUSED BY SMALL INTESTINAL BACTERIAL OVERGROWTH

• US 20110171232A1
• Filed: 03/28/2011
• Published: 07/14/2011
• Est. Priority Date: 08/11/1999
• Status: Active Grant

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Lin, Henry C., Pimentel, Mark
• Granted Patent: US 8,197,805 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/164 of a carboxylic acid with an aminoalcohol, e.g. ceramides
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• 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 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/545 Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61P 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• 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 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: C12Q 1/00 : Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 2800/065 : Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
• CPC Class Codes: G01N 33/56911 : Bacteria
• CPC Class Codes: H04L 67/125 : involving control of end-device applications over a network
• CPC Class Codes: H04L 69/08 : Protocols for interworking; Protocol conversion

Abstract

Disclosed is a method of diagnosing autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus, which involves detecting the presence of small intestinal bacterial overgrowth (SIBO) in a human subject having at least one symptom associated with a suspected diagnosis an autoimmune disease. Also disclosed is a method of treating these autoimmune diseases, which involves at least partially eradicating a SIBO condition in the human subject. The method includes administration of antimicrobial or probiotic agents, or normalizing intestinal motility by employing a prokinetic agent. Also disclosed is a kit for the diagnosis or treatment of autoimmune diseases.

Claims

1. A method of treating an autoimmune disease in a subject having a symptom associated with a suspected diagnosis of the autoimmune disease, comprising:

providing a composition comprising an antimicrobial agent or a probiotic agent; and

;

administering the composition to the subject to at least partially eradicate small intestinal bacterial overgrowth, whereby the symptom is improved.

2. The method of claim 1, further comprising:

detecting the presence of small intestinal bacterial overgrowth in the subject.

3. The method of claim 1, wherein the autoimmune disease is multiple sclerosis or systemic lupus erythematosus.

4. The method of claim 1, wherein the antimicrobial agent is selected from the group consisting of neomycin, metronidazole, teicoplanin, ciprofloxacin, doxycycline, tetracycline, augmentin, cephalexin, penicillin, ampicillin, kanamycin, rifamycin, rifaximin, vancomycin, and combinations thereof.

5. The method of claim 1, wherein the antimicrobial agent is rifaximin.

6. The method of claim 1, wherein the antimicrobial agent is a 4-amino salicylate compound or a 5 -aminosalicylate compound.

7. The method of claim 1, wherein the probiotic agent is Bifidobacterium sp., Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus paracasei subsp. paracasei, or Lactobacillus casei Shirota.

8. The method of claim 1, further comprising administering to said human subject an antagonist of a pro-inflammatory cytokine or an antibody that specifically binds an inflammatory cytokine, substantially simultaneously with or after at least partially eradicating small intestinal bacterial overgrowth in the human subject.

9. The method of claim 1, further comprising administering to said human subject an anti-inflammatory cytokine or an agonist thereof, substantially simultaneously with or after at least partially eradicating small intestinal bacterial overgrowth in the human subject.

10. A method of diagnosing an autoimmune disease, comprising:

detecting the presence of small intestinal bacterial overgrowth in a human subject having at least one symptom associated with a suspected diagnosis of an autoimmune disease, whereby the suspected diagnosis of an autoimmune disease is corroborated by the presence of small intestinal bacterial overgrowth.

11. The method of claim 10, wherein the autoimmune disease is multiple sclerosis or systemic lupus erythematosus.

12. The method of claim 10, wherein detecting the presence of a bacterial overgrowth is by analyzing the content of a gas mixture, said gas mixture being at least partially produced by the intestinal microflora of said human subject and being exhaled by said human subject after ingesting a controlled quantity of a substrate.

13. The method of claim 12, wherein the substrate is an isotope-labeled sugar or a sugar that is incompletely digested by a human.

14. The method of claim 13, wherein the sugar is glucose, lactose, lactulose or xylose.

15. The method of claim 12, wherein the content of methane, carbon dioxide, or hydrogen gas in the exhaled gas mixture is analyzed.

16. The method of claim 12, wherein analyzing the exhaled gas mixture is by gas chromatography.

17. The method of claim 13, wherein the sugar is an isotope-labeled sugar;

and analyzing the exhaled gas mixture is by mass spectrometry or radiation detection.

18. The method of claim 10, wherein detecting the presence of a bacterial overgrowth is by intestinal sampling from said human subject.

19. A kit for the diagnosis or treatment of an autoimmune disease, comprising:

at least one breath sampling container;

a pre-measured amount of a substrate; and

instructions for a user in corroborating a suspected diagnosis of an autoimmune disease and in the treatment thereof by detecting and treating small intestinal bacterial overgrowth.

20. The kit of claim 19, wherein the pre-measured substrate is isotope-labeled or poorly digestible by a human.

21. The kit of claim 19, wherein the pre-measured substrate is glucose, lactose, lactulose or xylose.

22. The kit of claim 19, further comprising an antimicrobial agent or probiotic agent.

23. The kit of claim 22, wherein the antimicrobial agent is neomycin, metronidazole, teicoplanin, ciprofloxacin, doxycycline, tetracycline, augmentin, cephalexin, penicillin, ampicillin, kanamycin, rifamycin, rifaximin, vancomycin, or a 4- or 5-aminosalicylate compound.

24. The kit of claim 22, wherein the antimicrobial agent is rifaximin.

25. The kit of claim 22, wherein the probiotic agent is Bifidobacterium sp., Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus paracasei subsp. paracasei, or Lactobacillus casei Shirota.

26. The kit of claim 19, further comprising a prokinetic agent.

27. The kit of claim 19, further comprising an antagonist of a pro-inflammatory cytokine or an antibody that specifically binds a pro-inflammatory cytokine

28. The kit of claim 19, further comprising an anti-inflammatory cytokine or an agonist thereof.

29. The kit of claim 19, further comprising an agent that modifies afferent neural feedback or sensory perception.