Compositions and methods for promoting growth of beneficial microbes to treat or prevent disease or prolong life

Patent metadata

Field	Value
Publication number	US-10028983-B2
Application number	US-201414769734-A
Country	US
Kind code	B2
Filing date	Feb 19, 2014
Priority date	Feb 22, 2013
Publication date	Jul 24, 2018
Grant date	Jul 24, 2018

Abstract

Inoculation of ATM-deficient mice with probiotic microorganisms, such as L. johnsonii, changed immune parameters, decreased a marker of DNA damage and increased the lifespan of the mice. Compositions and methods described herein are useful for the treatment and prevention of Ataxia telangiectasia and other cancer-prone diseases, such as p53 deficiency-associated cancers. Compositions and methods of the present invention are also useful for treating and preventing radiation-induced toxicity to normal tissue in a subject being exposed to radiation. Compositions and methods of the invention can increase lifespan in a simple, non-invasive manner.

First claim

The invention claimed is:

1. A method for treating, preventing, or delaying the onset of an ataxia telangiectasia (AT)-associated condition, a p53 deficiency, a cancerous condition in a subject having a p53 deficiency, a lung cancer, a sarcoma, a gastrointestinal cancer, a cancer of the genitourinary tract, a liver cancer, a skin cancer, a gynecological cancer, a bone cancer, a cancer of the nervous system, a hematologic cancer, a cancer of the adrenal glands, or a cancer associated with Li Fraumeni Disease, and/or exposure to radiation, in a subject, the method comprising:
administering to the subject a therapeutically effective amount of a composition comprising Lactobacillus johnsonii 456 as deposited at ATCC Deposit Designation No. PTA-124205;
whereby the disease related to genome instability, the ataxia telangiectasia (AT)-associated condition, the p53 deficiency, the cancerous condition in the subject having a p53 deficiency, and/or the exposure to radiation, in the subject is treated or, prevented, or its onset is delayed.

2. The method according to claim 1 , wherein the AT-associated condition is selected from a neurological degeneration a condition selected from inability or difficulty of the subject to walk, inability or difficulty of the subject to move, inability or difficulty of the subject to swallow, an immunodeficiency, an inflammatory condition a substantially increased expression level of transforming growth factor type beta, a substantially increased expression level of interleukin (IL)-10, a substantially increased expression level of IL-4, a substantially decreased expression level of myeloid differentiation primary response 88, a substantially decreased expression level of IL-12, a substantially decreased expression level IL-1β, or a substantially decreased expression level of interferon gamma; wherein the substantially increased and substantially decreased expression levels are in comparison to the respective expression levels in a subject not having AT, an inflammation-induced genotoxicity, a radiation sensitivity, an abundance of hepatic and/or migratory cells, a genetic instability, Nijmegen Breakage Syndrome, Fanconi's anemia, Werner Syndrome, Blooms Syndrome, or Li Fraumeni Disease a cancerous condition, hematologic cancer or a lymphoid malignancy.

3. A method for treating, mitigating, or preventing normal tissue damage in a subject being exposed to radiation in a subject, the method comprising:
administering to the subject a therapeutically effective amount of a composition comprising Lactobacillus Johnsonii 456 as deposited at ATCC Deposit Designation No. PTA-124205.

4. The method according to claim 3 , comprising both:
(a) administering to the subject a therapeutically effective amount of a composition comprising Lactobacillus johnsonii 456; and
(b) inhibiting the growth of one or more detrimental microorganisms in the subject.

5. The method according to claim 1 , comprising both:
(a) administering to the subject a therapeutically effective amount of a composition comprising Lactobacillus johnsonii 456; and
(b) inhibiting the growth of one or more detrimental microorganisms in the subject.

6. The method according to claim 5 , wherein step (b) comprises administering to the subject a therapeutically effective amount of an antibiotic.

7. The method according to claim 5 , wherein step (b) comprises administering to the subject a therapeutically effective amount of one or more bacteriophages.

8. The method according to claim 7 , wherein the one or more bacteriophages target a detrimental microorganism in Enterobacter, Helicobacter, Pseudomonas, Escherichia, Klebsiella, Staphylococcus, Proteus, Salmonella , or Shigella genera, or Dysgonomonas gadei, Prevotellaceae bacterium P4P_62 , Belliella sp. MIM10 , Parabacteroides merdae, Clostridium sp. AN-AS17 , Capnocytophaga ochracea, Pedobacter koreensis, Eubacterium sp. BU014 , Riemerella anatipestifer, Helicobacter typhlonicus, Petrimonas sulfuriphila, Caminicella sporogenes, Nubsella zeaxanthinifaciens, Porphyromonas sp. MI10-1288x, Sphingobacterium sp. NBRC 15338 , Proteiniphilum acetatigenes, Parabacteroides goldsteinii, Bacteroidetes bacterium P073B, Porphyromonas catoniae , and Bacteroides nordii.

9. The method according to claim 7 , wherein step (b) comprises administering to the subject a therapeutically effective amount of a combination of bacteriophages.

10. The method according to claim 9 , wherein the combination of bacteriophages targets the same detrimental microorganism.

11. The method according to any one of claim 7 , wherein the probiotic microorganism and the one or more bacteriophages are administered in the same composition.

12. A composition comprising a therapeutically effective amount of Lactobacillus johnsonii 456 as deposited at ATCC Deposit Designation No. PTA-124205 and one or more bacteriophages, wherein the therapeutically effective amount of the probiotic microorganism and one or more bacteriophages, is an amount sufficient to treat, prevent, or delay the onset of an ataxia telangiectasia (AT)-associated condition, a p53 deficiency, or exposure to radiation.

13. The composition according to claim 12 , wherein the one or more bacteriophages target a detrimental microorganism in Enterobacter, Helicobacter, Pseudomonas, Escherichia, Klebsiella, Staphylococcus, Proteus, Salmonella , or Shigella genera, or Dysgonomonas gadei, Prevotellaceae bacterium P4P_62 , Belliella sp. MIM10 , Parabacteroides merdae, Clostridium sp. AN-AS17 , Capnocytophaga ochracea, Pedobacter koreensis, Eubacterium sp. BU014 , Riemerella anatipestifer, Helicobacter typhlonicus, Petrimonas sulfuriphila, Caminicella sporogenes, Nubsella zeaxanthinifaciens, Porphyromonas sp. MI10-1288x, Sphingobacterium sp. NBRC 15338 , Proteiniphilum acetatigenes, Parabacteroides goldsteinii, Bacteroidetes bacterium P 073B, Porphyromonas catoniae , and Bacteroides nordii.

14. The method according to claim 8 , wherein the detrimental microorganism is Enterobacter cloacae, Helicobacter acinonychis, Helicobacter anseris, Helicobacter aurati, Helicobacter bilis, Helicobacter bizzozeronii, Helicobacter brantae, Helicobacter canadensis, Helicobacter canis, Helicobacter cetorum, Helicobacter cholecystus, Helicobacter cinaedi, Helicobacter cynogastricus, Helicobacter felis, Helicobacter fennelliae, Helicobacter ganmani, Helicobacter hepaticus, Helicobacter mesocricetorum, Helicobacter marmotae, Helicobacter muridarum, Helicobacter mustelae, Helicobacter pametensis, Helicobacter pullorum, Helicobacter pylori, Helicobacter rappini, Helicobacter rodentium, Helicobacter salomonis, Helicobacter trogontum, Helicobacter typhlonius, Helicobacter winghamensis, Salmonella enterica, Salmonella bongori, Salmonella subterranean, Salmonella typhimurium, Shigella dysenteriae, Shigella flexneri, Shigella boydii , and Shigella sonnei.

15. The method according to claim 14 , wherein the detrimental microorganism is Enterobacter cloacae, Helicobacter acinonychis, Helicobacter anseris, Helicobacter aurati, Helicobacter bilis, Helicobacter bizzozeronii, Helicobacter brantae, Helicobacter canadensis, Helicobacter canis, Helicobacter cetorum, Helicobacter cholecystus, Helicobacter cinaedi, Helicobacter cynogastricus, Helicobacter fells, Helicobacter fennelliae, Helicobacter ganmani, Helicobacter hepaticus, Helicobacter mesocricetorum, Helicobacter marmotae, Helicobacter muridarum, Helicobacter mustelae, Helicobacter pametensis, Helicobacter pullorum, Helicobacter pylori, Helicobacter rappini, Helicobacter rodentium, Helicobacter salomonis, Helicobacter trogontum, H

Assignees

• Univ California

Inventors

• Yamamoto Mitsuko L
• Schiestl Robert H
• Reliene Ramune
• Borneman James
• Presley Laura L
• Braun Jonathan

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/04

  Antibacterial agents · CPC title