Compositions of microbiota and methods related thereto

• US 10,729,732 B2
• Filed: 10/30/2019
• Issued: 08/04/2020
• Est. Priority Date: 02/29/2012
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Johnson & Johnson Consumer Inc. (Johnson & Johnson)
• Original Assignee: Ethicon Endo-Surgery, Inc. (Johnson & Johnson)
• Inventors: Kaplan, Lee M., Liou, Alice P., Turnbaugh, Peter J., Harris, Jason L.
• Primary Examiner(s): Paguio Frising, Michelle F.
• Application Number:
  US16/669,143
• Publication Number:
  US 20200121732A1
• Time in Patent Office: 279 Days
• Field of Search: None
• CPC Class Codes: A61K 2035/11 Medicinal preparations comprising living procariotic cells
• 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 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• 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 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C12Q 1/689 : for bacteria
• 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

Methods and compositions are provided for treating weight related conditions and metabolic disorders by altering microbiota in a subject. One aspect provides methods and compositions to alter microbiota in a subject by administering to the subject a composition that includes a substantially purified microbiota from phyla such as Bacteroidetes, Proteobacteria, Firmicutes and Verrucomicrobia or orders such as Bacteroidales, Verrucomicrobiales, Clostridiales and Enterobacteriales or genera such as Alistipes, Clostridium, Escherichia, and Akkermansia. Another aspect includes a pharmaceutical composition for altering microbiota that includes a therapeutically effective amount of substantially purified microbiota and a pharmaceutically acceptable carrier. Yet another aspect includes methods for treating a disorder, such as obesity, in a subject in need of such treatment by changing relative abundance of microbiota in a gastrointestinal tract of the subject without or in addition to a surgical procedure.

Claims

1. A method of lowering triglycerides in a subject in need thereof, the method comprising orally administering a composition comprising a therapeutically effective amount of bacteria comprising substantially purified Akkermansia to the subject, thereby lowering triglycerides in the subject, wherein the substantially purified Akkermansia comprises at least 50% of a strain of Akkermansia.

2. The method of claim 1, wherein a serum triglyceride level is decreased in the subject.

3. The method of claim 1, wherein the subject does not decrease food intake.

4. The method of claim 1, wherein viable cells of the Akkermansia are administered to the subject.

5. The method of claim 1, wherein the substantially purified Akkermansia is co-administered with one or more additional probiotic strains.

6. The method of claim 1, wherein if the bacteria comprise a mixture of bacterial strains, then at least 50% of the bacterial strains in the composition are Verrucomicrobia, Bacteroidetes, Firmicutes, or Proteobacteria.

7. The method of claim 1, wherein the bacteria further comprise at least one of a substantially purified Bacteroidetes, a substantially purified Firmicutes, or a substantially purified Proteobacteria.

8. The method of claim 1, wherein the bacteria further comprise substantially purified Clostridiales.

9. The method of claim 1, wherein the bacteria further comprise substantially purified Clostridium.

10. The method of claim 1, wherein the composition further comprises one or more prebiotics.

11. The method of claim 1, wherein the composition is co-administered with one or more prebiotics.

12. The method of claim 11, wherein the one or more prebiotics comprises a fructooligosaccharide, a glucooligosaccharide, a xylooligosaccharide, a galactooligosaccharide, an arabinoxylan, an arabinogalactan, a galactomannan, a polydextrose, an inulin, a derivative thereof, or a combination thereof.

13. The method of claim 1, wherein the composition further comprises a coating, wherein the coating does not begin to degrade until after it exits a stomach of the subject.

14. The method of claim 1, wherein the relative abundance of the Akkermansia strain in the subject is increased by at least 5%.

15. The method of claim 1, wherein the Akkermansia is lyophilized.

16. The method of claim 1, wherein the composition is administered in one or more doses per day.

17. The method of claim 1, wherein the composition is administered in one to three doses per day.

18. The method of claim 1, wherein the composition is administered at a dose of from about 0.001 to about 100 mg/kg body weight of the subject.

19. The method of claim 1, wherein the composition is administered at a dose of from about 0.01 to about 50 mg/kg body weight of the subject.

20. The method of claim 1, wherein the composition is administered at a dose of from about 0.05 to about 10 mg/kg body weight of the subject.