CN-121975657-A - Application of outer membrane vesicles from microorganisms in medicines for treating obesity and related metabolic diseases

Abstract

The invention discloses application of an outer membrane vesicle from a microorganism in medicines for treating obesity and related metabolic diseases, and belongs to the technical field of exosomes. The technical problems to be solved are that probiotics beneficial to intestinal tracts have weak colonization ability in the intestinal tracts, are easily influenced by gastrointestinal tract environment and have unstable individual response, and the technical scheme is that the outer membrane vesicle containing sphingosine and being sourced from microorganisms is provided, wherein the content of the sphingosine in the outer membrane vesicle is 50-65 ng/mg.

Inventors

• CHENG FANG
• LV GUOWEN
• CHEN HONGBO
• WU HUIXING
• SU DANDAN

Assignees

• 中山大学·深圳
• 中山大学

Dates

Publication Date

20260505

Application Date

20260202

Claims (10)

1. 1. An outer membrane vesicle comprising sphingosine, wherein the sphingosine content of the outer membrane vesicle is 50-65 ng/mg.
2. 2. The outer membrane vesicle of claim 1, wherein the outer membrane vesicle is derived from bacteroides parapsilosis.
3. 3. The outer membrane vesicle of claim 2, wherein the parabacteroides comprises parabacteroides aureoides Parabacteroides goldsteinii JCM 13446 or parabacteroides diradii Parabacteroides distasonis ATCC 8503.
4. 4. A method for preparing the outer membrane vesicle according to claim 1, comprising culturing Paralopecias aurea or Paralopecias parapsilosis, collecting culture supernatant, and separating to obtain the outer membrane vesicle.
5. 5. A composition comprising the outer membrane vesicle of any one of claims 1-3 and a pharmaceutically acceptable carrier.
6. 6. Use of an outer membrane vesicle according to any one of claims 1-3 or a composition according to claim 5 for the preparation of a medicament for the prevention or treatment of a metabolic disorder.
7. 7. The use according to claim 6, wherein the metabolic disease comprises obesity, diabetes, hyperuricemia, hypertension, hyperlipidemia, hyperglycemia, metabolic syndrome, nonalcoholic fatty liver, insulin resistance, atherosclerosis, or inflammatory skin disease.
8. 8. The use according to claim 6, wherein the medicament comprises a lipid accumulation inhibiting medicament, an anti-inflammatory medicament, an antioxidant medicament, an insulin sensitivity improving medicament or a mitochondrial function enhancing medicament.
9. 9. The use according to claim 6, further comprising the use in combination with a metabolic or anti-inflammatory drug.
10. 10. The use according to claim 9, wherein the metabolic class of drug comprises metformin or a GLP-1 receptor agonist and the anti-inflammatory class of drug comprises an IL-17 inhibitor.

Description

Application of outer membrane vesicles from microorganisms in medicines for treating obesity and related metabolic diseases Technical Field The invention belongs to the technical field of exosomes, and particularly relates to application of outer membrane vesicles derived from microorganisms in medicines for treating obesity and related metabolic diseases. Background For understanding the technical content of the present invention: Intestinal flora serves as a "second genome" and is involved in the development of obesity by regulating energy absorption, short Chain Fatty Acid (SCFAs) synthesis, and inflammatory signaling pathways. Studies have shown that a ‌ -firmicutes/bacteroides ratio imbalance ‌ in the intestinal tract of obese individuals results in decreased butyrate-producing bacteria and increased Lipopolysaccharide (LPS) producing bacteria, leading to metabolic endotoxemia and insulin resistance. Although the microecological intervention means represented by probiotics and prebiotics can relieve obesity by regulating flora, the effect of the microecological intervention means has strain specificity and an undefined action mechanism, and more targeted regulatory factors need to be mined. Specific strains ‌ such as Paralopecias aurea (Parabacteroides goldsteinii, pg) and Paralopecias diutanae (Parabacteroides distasonis, pd) are taken as key members of intestinal symbiotic bacteria, and researches indicate that the abundance is inversely related to obesity, and the anti-obesity effect can be exerted by enhancing the intestinal barrier function and inhibiting the expression of proinflammatory factors. The secreted ‌ Outer Membrane Vesicles (OMVs) ‌ are used as natural nano-carriers to deliver active molecules such as proteins, nucleic acids and the like, and mediate flora-host communication. OMVs have low immunogenicity, high stability and biological barrier crossing capability, exhibit unique advantages in regulating host immune metabolism (such as TLR signal path activation and macrophage polarization), and provide novel drug delivery systems and action targets for obesity treatment. There is no report on the disclosures of Parabacteroides distasonis and Parabacteroides goldsteinii-derived OMVs in obesity and related metabolic diseases. Meanwhile, the active ingredients of OMVs still lack explicit recognition and mechanism resolution. Therefore, the development of the functional characteristics of Parabacteroides distasonis and Parabacteroides goldsteinii-derived OMVs, the identification of key metabolites thereof and the exploration of the mechanism of action thereof will provide a new therapeutic strategy for obesity and related metabolic syndromes, a theoretical basis for developing targeted delivery systems or flora combination therapies based on ‌ engineering OMVs ‌, and a paradigm shift of pushing obesity intervention strategies from "rough flora regulation" to "precise nanotherapeutics". The related patent documents: Publication No. CN114401727a, publication No. 2022.04.06, in state of the art, discloses a method for treating a metabolic disease or disorder in a mammalian subject comprising administering to the gastrointestinal system of the subject a composition, wherein the composition comprises inactivated parabacteroides aureotides (Parabacteroides goldsteinii), growth medium of parabacteroides aureotides, or vesicles from parabacteroides aureotides. Publication No. CN117159592A, publication No. 2023.12.05, discloses application of extracellular vesicles derived from Paralopecuroides dirachta in relieving diseases caused by high-fat diet, and can be used for relieving diseases caused by high-fat diet such as hyperlipidemia, hypertension, fatty liver, obesity and diabetes. The relevant non-patent literature: Journal name or book name "Cell Reports", literature name "Parabacteroides distasonisAlleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids", volume No. Vol 26, publication date 2019.1.2, which discloses that parabacteroides diri exert multi-target global regulation by generating succinic acid and secondary cholic acid through activating different signal pathways, and can significantly improve obesity, insulin resistance, lipid metabolism disorder and nonalcoholic fatty liver symptoms in high-fat Diet Induced Obese (DIO) mice and ob/ob obese model mice. Disclosure of Invention The invention aims to provide that: An application of outer membrane vesicles from microorganism in preparing medicines for treating obesity and related metabolic diseases, and related technology thereof are provided, which can solve the technical problems of weak colonization ability of probiotics beneficial to intestinal tract in intestinal tract, susceptibility to gastrointestinal tract environment, unstable individual response, etc., or the combination thereof. The patent provides an application of an outer membrane vesicle (Parabacteroides goldsteinii outer membran