Granted Patent
B2
US 12,329,786 · App. 18/335,889 · Granted Jun 17, 2025
Regulate gut microbiota to treat neurodegenerative disorders
Assignee:
CALIFORNIA INSITUTE OF TECHNOLOGY
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Abstract
Disclosed herein are methods and compositions that can be used to improve motor deficits and neuroinflammation in subjects in need, for example subjects suffering from neurodegenerative disorders (e.g., Parkinson's disease). Also disclosed are methods and compositions that can be used to diagnose neurodegenerative disorders, such as Parkinson's disease.
Claims (24)
1. A method of reducing neuroinflammation in a subject having a disease, the method comprising:
administering a composition comprising an inhibitor of a short chain fatty acid (SCFA) comprising propionate or butyrate; and
increasing a level of a Parkinson's disease (PD)-protective bacteria in a gut microbiota of the subject; or
decreasing a level of a PD-enhancing bacteria in a gut microbiota of the subject,
wherein increasing the level of the PD-protective bacteria or decreasing the level of the PD-enhancing bacteria reduces neuroinflammation in the subject,
wherein the PD-protective bacteria is Lachnospiraceae, Rikenellaceae, Peptostreptococcaceae , or Butyricicoccus and
wherein the PD-enhancing bacteria belongs to Proteus species, Bilophila species, Roseburia species, Pseudoramibacter Eubacterium , or Veillonellaceae family.
2. The method of claim 1 , wherein the disease is a neurodegenerative disease.
3. The method of claim 1 , wherein the disease is PD, dementia with Lewy body disease, or multiple system atrophy.
4. The method of claim 1 , wherein increasing the level of the PD-protective bacteria in the gut microbiota of the subject comprises introducing gut microbiota from a healthy subject to the subject.
5. The method of claim 4 , wherein introducing gut microbiota from a healthy subject comprises fecal transplantation, microbiota conventionalization, microbial colonization, reconstitution of gut microbiota, probiotic treatment, or a combination thereof.
6. The method of claim 1 , further comprising administering one or more antibiotics to the subject.
7. The method of claim 6 , wherein the one or more antibiotics comprise ampicillin, vancomycin, neomycin, gentamycin, erythromycin, or any combination thereof.
8. The method of claim 1 , wherein reducing neuroinflammation comprises reducing TNF-α production, reducing interleukin-6 (IL-6), or reducing «Syn aggregation.
9. The method of claim 2 , wherein reducing neuroinflammation comprises reducing microglia activation in the subject.
10. The method of claim 2 , further comprising identifying the subject as having a disease when the subject has an abnormal level of aggregation of α-synuclein (αSyn).
11. The method of claim 10 , further comprising measuring a rate and/or level of αSyn aggregation in the brain of the subject, the clearance rate and/or level of insoluble αSyn protein aggregate in the brain of the subject, or a combination thereof.
12. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.
13. The method of claim 2 , wherein the composition is formulated for oral administration.
14. The method of claim 1 , wherein the method further comprises:
administering a composition comprising an inhibitor of a short chain fatty acid (SCFA) comprising propionate or butyrate;
increasing a level of a Parkinson's disease (PD)-protective bacteria in a gut microbiota of the subject; and
decreasing a level of a PD-enhancing bacteria in a gut microbiota of the subject,
wherein increasing the level of the PD-protective bacteria and decreasing the level of the PD-enhancing bacteria reduces neuroinflammation in the subject.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 14, 2025
From: MAZMANIAN, SARKIS K.; SAMPSON, TIMOTHY R.
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 071112/0581 →
Continuity (5)
Continuation
16302321
Provisional Application
62443952
· Jan 9, 2017
Provisional Application
62370578
· Aug 3, 2016
Provisional Application
62340408
· May 23, 2016
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