# US 2025/0375486 A1 · Regulate gut microbiota to treat neurodegenerative disorders

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- Number: US 2025/0375486 A1
- Document ID: US20250375486A1
- Status: Published application
- Kind: A1
- Application number: 19/212,317
- Filed: 2025-05-19
- Published: 2025-12-11
- Earliest claimed: 2016-05-23
- Assignees: California Institute of Technology
- Applicants: California Institute of Technology
- Inventors: Sarkis K. Mazmanian; Timothy R. Sampson
- Web page: https://patentgrep.com/patent/US20250375486A1

## CPC

- A61K 35/741: Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06)
- 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 [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems
- A61K 31/7036: having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/16: Anti-Parkinson drugs
- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/689: for bacteria
- G01N 33/56911: {Bacteria}
- G01N 2800/2835: Movement disorders, e.g. Parkinson, Huntington, Tourette
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## 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

### Claim 1

(canceled)

### Claim 2

A method for improving a motor deficit 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.

### Claim 3 (depends on 2)

The method of claim 2, wherein the disease is a neurodegenerative disease.

### Claim 4 (depends on 2)

The method of claim 2, wherein the disease is PD, dementia with Lewy body disease, or multiple system atrophy.

### Claim 5 (depends on 2)

The method of claim 2, wherein the PD-protective bacteria is Lachnospiraceae, Rikenellaceae, Peptostreptococcaceae, or Butyricicoccus

### Claim 6 (depends on 2)

The method of claim 2, wherein the PD-enhancing bacteria belongs to Proteus sp., Bilophila sp., Roseburia sp., Pseudoramibacter Eubacterium, or Veillonellaceae family.

### Claim 7 (depends on 2)

The method of claim 2, wherein the PD-enhancing bacteria belongs to KEGG family K00929, K01034, or K01035.

### Claim 8 (depends on 2)

The method of claim 2, 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.

### Claim 9 (depends on 8)

The method of claim 8, 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.

### Claim 10 (depends on 2)

The method of claim 2, further comprising administering one or more antibiotics to the subject.

### Claim 11 (depends on 10)

The method of claim 10, wherein the one or more antibiotics comprise ampicillin, vancomycin, neomycin, gentamycin, erythromycin, or any combination thereof.

### Claim 12 (depends on 2)

The method of claim 2, wherein motor deficit is tremors, muscle rigidity, bradykinesia, impaired gait, or any combination thereof.

### Claim 13 (depends on 2)

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).

### Claim 14 (depends on 13)

The method of claim 13, 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.

### Claim 15 (depends on 2)

The method of claim 2, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 16 (depends on 2)

The method of claim 2, wherein the composition is formulated for oral administration.

### Claim 17 (depends on 2)

The method of claim 2, 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 improves motor deficit in the subject.

### Claim 18

A method of diagnosing parkinsonism in a subject, comprising
determining the presence and/or level of one or more PD-associated bacterial species in the subject, whereby the presence and/or abnormal level of the one or more PD-associated bacterial species indicates that the subject has a risk of developing, or is suffering from a symptom of parkinsonism.

### Claim 19

A pharmaceutical composition, comprising
an inhibitor of a PD-enhancing microbial metabolite, and
one or more pharmaceutically acceptable carriers.
