# US 2023/0053778 A1 · Methods of promoting scfa production by gut microbiota

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- Number: US 2023/0053778 A1
- Document ID: US20230053778A1
- Status: Published application
- Kind: A1
- Application number: 17/769,125
- Filed: 2020-10-16
- Published: 2023-02-23
- Earliest claimed: 2019-10-18
- Assignees: Multigerm UK Enterprises Ltd.
- Applicants: Multigerm UK Enterprises Ltd
- Inventors: Barry SMITH; Michael BUTLER
- Web page: https://patentgrep.com/patent/US20230053778A1

## CPC

- A23L 33/135: Bacteria or derivatives thereof, e.g. probiotics
- A61K 35/747: Lactobacilli, e.g. L. acidophilus or L. brevis
- A23L 33/40: {Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula}
- A61K 35/744: Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 25/16: Anti-Parkinson drugs
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- 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
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- 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
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention relates to methods for promoting SCFA production by gut microbiota by administering a liquid, water-based probiotic composition. The methods are particularly effective at promoting gut health. The invention further relates to methods of promoting intestinal barrier integrity, methods of promoting a tolerogenic gut phenotype, and methods of treating Parkinson's Disease.

## Claims

### Claim 1

A method of stimulating production of one or more short chain fatty acids (SCFAs) by a subject's gut microbiota comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria.

### Claim 2

A method of promoting gastrointestinal health in a subject comprising administering a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria, wherein administration of the probiotic preparation promotes production of one or more short chain fatty acids (SCFAs) by the subject's gut microbiota, thereby promoting intestinal health.

### Claim 3 (depends on 1, 2)

A method according to claim 1 or claim 2 wherein the one or more SCFAs is selected from butyrate, propionate and acetate, preferably butyrate.

### Claim 4

A method of promoting growth of one or more bacterial phyla selected from Actinobacteria (e.g. Bifidobacteriaceae), Firmicutes (e.g. Veillonellaceae, Lachnospiraceae, Streptococcaceae, Eubacteriaceae, Ruminococcaceae, Erysipelotrichaceae, Clostridiaceae), Proteobacteria (e.g. Enterobacteriaceae) in the gut microbiota of a subject, the method comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria.

### Claim 5

A method of inhibiting growth of one or more bacterial phyla selected from Actinobacteria (e.g. Coriobacteriaceae, Eggerthellaceae), Bacteroidetes (e.g. Bacteroidaceae, Rikenellaceae, Lachnospiraceae, Ruminococcaceae), Firmicutes (e.g., Acidaminococcaceae, Enterococcaceae, Clostridiaceae, Peptostreptococcaceae), Proteobacteria (e.g. Enterobacteriaceae), Synergistetes (e.g. Synergistaceae) and Verrucomicrobio (e.g. Akkermansiaceae) in the gut microbiota of a subject, the method comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria

### Claim 6 (depends on 4, 5)

A method according to claim 4 or claim 5, wherein the effect on the growth of the one or more bacterial phyla is in the gut mucosal compartment.

### Claim 7 (depends on 4, 5, 6)

A method according to any one of claims 4-6, wherein the effect on the growth of the one or more bacterial phyla is in the gut luminal compartment.

### Claim 8

A method of promoting intestinal barrier integrity in a subject, the method comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria, wherein administration of the probiotic preparation promotes said intestinal barrier integrity.

### Claim 9 (depends on 8)

A method according to claim 8, wherein the method prevents or reduces loss of intestinal barrier integrity in a subject.

### Claim 10 (depends on 8, 9)

A method according to claim 8 or claim 9, wherein the subject is at risk of loss of intestinal barrier integrity.

### Claim 11 (depends on 8)

A method according to claim 8, wherein the method promotes intestinal barrier repair.

### Claim 12

A method for promoting a tolerogenic gut phenotype in a subject, the method comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria, wherein administration of the probiotic preparation promotes said tolerogenic gut phenotype.

### Claim 13

A method according to any one of the preceding claims wherein the method is a non-therapeutic method.

### Claim 14

A method according to any one of the preceding claims wherein the subject is a healthy individual.

### Claim 15

A method according to any one of the preceding claims wherein the subject is in a state of intestinal dysbiosis.

### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15)

A method according to any one of claims 1-12 and 15, wherein the method is a therapeutic method.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16)

A method according to any one of claims 1-12 and 15-16 wherein the subject has a condition selected from Parkinson's Disease, liver cirrhosis, inflammatory bowel disease (IBD), Clostridium difficile infection, MRSA infection, E. coli infection, salmonella infection, norovirus infection, giardiasis, coeliac disease, chronic kidney disease, HIV/AIDS, cystic fibrosis, type I diabetes, obesity, and chronic fatigue syndrome.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17)

A method according to any one of claims 1-12 and 15-17, wherein the subject has Parkinson's Disease.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17)

A method according to any one of claims 1-12 and 15-17, wherein the subject has liver cirrhosis.

### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17)

A method according to any one of claims 1-12 and 15-17, wherein the subject has IBD.

### Claim 21

A method of treating or preventing Parkinson's Disease in a subject, the method comprising administering to the subject a liquid, non-dairy probiotic preparation comprising a population of lactic acid bacteria.

### Claim 22 (depends on 21)

A method according to claim 21, wherein administration of the probiotic preparation improves in the subject one or more of: motor symptoms, non-motor symptoms, systemic inflammatory markers.

### Claim 23 (depends on 21, 22)

A method according to claim 21 or claim 22, wherein administration of the probiotic preparation improves non-motor symptoms in the subject, optionally improves gastrointestinal non-motor symptoms in the subject.

### Claim 24 (depends on 21, 22, 23)

A method according to any one of claims 21-23, wherein administration of the probiotic preparation improves intestinal barrier integrity.

### Claim 25 (depends on 21, 22, 23, 24)

A method according to any one of claims 21-24, wherein administration of the probiotic preparation improves intestinal barrier repair.

### Claim 26 (depends on 21, 22, 23, 24, 25)

A method according to any one of claims 21-25, wherein administration of the probiotic preparation promotes a tolerogenic gut phenotype in the subject.

### Claim 27 (depends on 21, 22, 23, 24, 25)

A method according to any one of claims 21-25 wherein administration of the probiotic preparation treats or prevents Parkinson's Disease in the subject by reducing the severity or slowing the progression of motor symptoms or by slowing or preventing the onset of motor symptoms.

### Claim 28 (depends on 21, 22, 23, 24, 25, 26)

A method according to any one of claims 21-26 wherein the subject is in a state of gastrointestinal dysbiosis, optionally wherein the subject is exhibiting an elevated level of Firmicutes and/or a reduced level of Bacteroidetes in their gut microbiota compared to healthy controls.

### Claim 29

A method according to any one of the preceding claims, wherein the method promotes production of one or more anti-inflammatory molecules by intestinal epithelial cells, optionally wherein the one or more anti-inflammatory molecules are selected from IL-6 and IL-10.

### Claim 30

A method according to any one of the preceding claims, wherein the method reduces production of one or more pro-inflammatory molecules by intestinal epithelial cells, optionally wherein the one or more pro-inflammatory molecules are selected from CXCL-10, TNFa, IL-8 and MCP-1.

### Claim 31 (depends on 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)

A method according to any one of claims 4-30, wherein the method promotes production of one or more SCFAs, preferably acetate, propionate or butyrate, preferably butyrate.

### Claim 32

A method according to any one of the preceding claims wherein the population of lactic acid bacteria comprises one or more of Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus plantarum and Enterococcus faecium bacteria.

### Claim 33

A method according to any one of the preceding claims wherein the population of lactic acid bacteria comprises each of Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus plantarum and Enterococcus faecium bacteria.

### Claim 34

A method according to any one of the preceding claims wherein the method reduces production of one or more branched chain fatty acids (BCFA) and/or ammonium by the subject's gut microbiota

### Claim 35 (depends on 34)

A method according to claim 34 wherein the one or more BCFAs is selected from isobutyrate, isovalerate and 2-methylbutyrate.

### Claim 36

A method according to any one of the preceding claims wherein the probiotic composition is administered to the subject at least once a week, preferably once a day.

### Claim 37

A method according to any one of the preceding claims wherein the probiotic composition is administered to the subject for a period of at least 1 month, at least 2 months or at least 3 months.
