US-12617755-B2 - Compositions and methods for treating metabolic disease

Abstract

The present disclosure relates to compounds, compositions and supplements that are capable of treating obesity. The disclosure further relates to methods of treating obesity in a subject in need thereof.

Inventors

• Arpana Church
• Tien Dong
• Emeran A. Mayer
• Jonathan P. Jacobs

Assignees

• THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Dates

Publication Date

20260505

Application Date

20200803

Claims (15)

1. 1 . A pharmaceutical composition comprising at least one bacterial strain from the genus of Akkermansia , at least one bacterial strain from the genus Bacteroides , a pharmaceutically acceptable excipient, and a compound, wherein the compound is (indole-3-propanoic acid) or a salt thereof.
2. 2 . The composition of claim 1 , wherein the bacterial strain further comprises Bacteroides.
3. 3 . The composition of claim 1 , wherein the bacterial strain further comprises Clostridiales.
4. 4 . The composition of claim 1 , wherein the bacterial strain further comprises Faecalibacterium.
5. 5 . The composition of claim 1 , wherein the bacterial strain further comprises Faecalibacterium prausnitzii.
6. 6 . The composition of claim 1 , wherein the bacterial strain further comprises Ruminoccoccus.
7. 7 . A food supplement comprising at least one bacterial strain from the genus Akkermansia , at least one bacterial strain from the genus Bacteroides , and a compound, wherein the compound is (indole-3-propanoic acid) or a salt thereof.
8. 8 . The food supplement of claim 7 , wherein the food supplement comprises Akkermansia muciniphila.
9. 9 . The food supplement of claim 7 , wherein the bacterial strain further comprises Bacteroides.
10. 10 . The food supplement of claim 7 , wherein the bacterial strain further comprises Clostridiales.
11. 11 . The food supplement of claim 7 , wherein the bacterial strain further comprises Faecalibacterium.
12. 12 . The food supplement of claim 7 , wherein the bacterial strain further comprises Faecalibacterium prausnitzii.
13. 13 . The food supplement of claim 7 , wherein the bacterial strain further comprises Ruminoccoccus.
14. 14 . A method of treating obesity in a subject, comprising administering to a subject in need thereof the food supplement of claim 7 .
15. 15 . The method of claim 14 , wherein the subject has an increased number of bacteria from a bacterial strain selected from the genus of Megamonas as compared to an individual with a healthy weight.

Description

RELATED APPLICATIONS This application is the § 371 U.S. National-Stage application of PCT/US2020/044749, filed Aug. 3, 2020, which claims the benefit of U.S. Provisional Patent Application No. 62/885,010, filed on Aug. 9, 2019. The contents of each of these applications are hereby incorporated by reference in their entirety. GOVERNMENT SUPPORT This invention was made with government support under DK048351, DK041301, DK121025, DK007180, DK106528 and TR001881, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND Obesity has reached global epidemic proportions and has become one of the leading preventable causes of death in the United States, for example in 2008, an estimated 500 million adults worldwide were considered obese. Obesity is associated with many comorbidities, such as diabetes, cancer(s), premature mortality from cardiovascular disease (CVD), and musculoskeletal disorders. In addition to the health detriments, the economic and social consequences of obesity are compounding. For instance, in 2011, medical costs associated with treatment of preventable diseases associated with obesity were estimated to increase by $48-66 billion/year in the U.S. alone, with an estimated 65 million more adults to become obese by 2030.5 Accordingly, there is an ongoing need for new treatments for obesity. SUMMARY OF THE INVENTION Provided herein are compounds, compositions, food supplements and methods for treating obesity and/or food addiction. In one aspect, the present disclosure provides compounds of formula I: or a pharmaceutically acceptable salt thereof, whereinX is O, NR3, or S;R1 is alkyl, wherein the alkyl is optionally substituted, e.g., with hydroxyl, thio, sulfonamido, carbamate, carboxy, ester, or amido;each R2 is independently selected from alkyl, halo, hydroxyl, carboxyl, acyl, ester, thioester, alkoxy, phosphoryl, amino, amido, cyano, nitro, azido, alkylthio, alkenyl, alkynyl, cycloalkyl, heterocyclylalkyl, heteroaralkyl, sulfonamide, aryl, heteroaryl, heterocyclyl, and aralkyl;R3 is hydrogen or alkyl; andn is 0-4. In another aspect, the present disclosure provides a pharmaceutical composition comprising at least one bacterial strain selected from the genuses of Akkermansia, Bacteroides, Clostridiales, Ruminoccoccus, and Faecalibacterium and at least one pharmaceutically acceptable excipient. In yet another aspect, the present disclosure provides a food supplement comprising at least one bacterial strain selected from the genuses of Akkermansia, Bacteroides, Clostridiales, Ruminoccoccus, and Faecalibacterium. In yet another aspect, the present disclosure provides a pharmaceutical composition comprising at least one bacterial strain selected from the genuses of Akkermansia, Bacteroides, Clostridiales, Ruminoccoccus, and Faecalibacterium, a compound of formula I, and at least one pharmaceutically acceptable excipient. In yet another aspect, the present disclosure provides a food supplement comprising at least one bacterial strain selected from the genuses of Akkermansia, Bacteroides, Clostridiales, Ruminoccoccus, and Faecalibacterium and a compound of formula I. In yet another aspect, the present disclosure provides method of treating obesity and/or food addiction with the compounds, compositions, and food supplements of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A shows a partial least square discriminant analysis of gut microbiome composition between patients with food addiction versus those without along with their 95% confidence ellipses. FIG. 1B shows a contribution plot indicating genera contributing to sPLS-DA plot that discriminate between the two groups of FIG. 1A. FIG. 2A shows Alpha diversity metrics (Chao1, Shannon, and Faith's Index) between patients high with a high YFAS vs. those with a low YFAS. FIG. 2B shows Alpha diversity metrics (Chao1, Shannon, and Faith's Index) between patients high with a high BMI vs. those with a low BMI. FIG. 3A shows a phylum taxonomic gut bacteria profile of subjects with a high YFAS vs. those with a low YFAS score. FIG. 3B shows a genus taxonomic gut bacteria profile of subjects with a high YFAS vs. those with a low YFAS score. FIG. 3C depicts a DESEq2 analysis showing the OTUs that were correlated to YFAS score. FIG. 4 shows the communication between the intraparietal sulcus/transverse parietal sulcus to the putamen of subjects with a low YFAS score vs. those with a high YFAS score. FIG. 5A shows a receiver operator curve for the random forest classifier at identifying patients with food addiction. FIG. 5B shows a variable importance plot of the factors most important in the random forest classifier at predicting food addiction. FIG. 6A shows taxonomic profiles between subjects with No Food Addiction (No FA) and Food Addiction (FA) on a phylum level. Only taxa ≥1% relative abundance are shown. FIG. 6B shows taxonomic profiles between subjects with No Food Addiction (No FA) and Food