Use of bacteroides in the prevention and treatment of coronary artery disease

Abstract

Use of a Bacteroides bacterial strain in the manufacture of a preparation for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject. A preparation comprising a Bacteroides bacterium, such as a pharmaceutical composition, a nutraceutical composition, or a food composition. A method for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, the method comprising the step of administering to a subject in need thereof an effective amount of a Bacteroides bacterial strain.

Description

[0001] Cross-reference to related applications

[0002] none

[0003] field

[0004] This invention relates to microbiology. Specifically, it relates to the use of Bacteroides strains in the preparation of formulations for treating and / or preventing coronary artery disease in subjects, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions. The invention also relates to formulations comprising Bacteroides (such as pharmaceutical compositions, nutritional pharmaceutical compositions, or food compositions). Furthermore, the invention relates to a method for treating and / or preventing coronary artery disease, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions in subjects, the method comprising the step of administering an effective amount of a Bacteroides strain to a subject in need of such treatment.

[0005] background

[0006] Coronary artery disease (CAD) refers to any abnormal condition of the coronary arteries that interferes with the delivery of an adequate blood supply to the myocardium or any part thereof. Typically, CAD is caused by the accumulation of plaque on the arterial walls (i.e., atherosclerosis), particularly in the large and medium-sized arteries that serve the heart. These conditions share similar causes, mechanisms, and treatments. CAD represents a leading cause of death and morbidity worldwide.

[0007] Current knowledge indicates that genetic and environmental factors and their interactions synergistically induce complex phenotypes and many diseases. Coronary artery disease (CAD), as one of the most influential complex diseases, has been increasingly studied in recent years through GWAS (genome-wide association studies), revealing that 10.6% of genetic factors are represented by 46 common variants (Ehret, GB, et al., Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103-109, incorporated herein by reference). However, more knowledge is still needed regarding the influence of environmental factors such as gut microbiota and the contributions of genes and microbes to disease.

[0008] Our "forgotten organ," the gut microbiota, plays a vital role in many ways to our health, such as obtaining energy from food, producing important metabolites, promoting the development and maturation of the immune system, and protecting the host from pathogen infection. Recent studies have shown that dysbiosis, chronic inflammation, and metabolic abnormalities exist in the gut of certain metabolic diseases such as diabetes and obesity. Coronary artery disease is characterized by inflammation, oxidation, and lipid metabolism, which may be potentially related to gut microbes and their metabolites. A recent study showed that gut microbes can metabolize red meat components (such as L-carnitine, phosphatidylcholine, and cholesterol) into TMA, which is further oxidized in the liver to TMAO, thereby inducing an oxidative reaction in the blood vessels, leading to inflammation and lipid deposition, ultimately causing atherosclerosis and coronary heart disease. Meanwhile, the gut microbiota of patients with symptomatic atherosclerosis showed significant abnormalities compared to healthy subjects (Koeth, RA, et al., Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine 19, 576-585, incorporated herein by reference). These studies indicate that gut microbiota dysbiosis can significantly influence the pathogenesis of coronary artery disease by inducing metabolic abnormalities in humans. However, the role of gut microbiota dysbiosis in the pathogenesis of atherosclerotic coronary artery disease and its impact on the metabolic system remain perplexing.

[0009] summary

[0010] This disclosure aims to address, at least to some extent, at least one problem existing in the prior art.

[0011] This invention is based, at least in part, on the following findings of the inventors.

[0012] The assessment and characterization of the gut microbiota has become a major research area in human diseases, including coronary artery disease (CAD). To analyze the gut microbiota content in CAD patients, the inventors conducted a metagenomic association study (MGWAS) based on deep shotgun sequencing of gut microbial DNA samples from 165 individuals (Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55-60 (2012), incorporated herein by reference).

[0013] The inventors identified two species of Bacteroides probiotics. They then verified the effects of these two Bacteroides probiotics on CAD in animal experiments. The results of the animal experiments demonstrated the effective prevention and treatment of CAD by Bacteroides uniformis and Bacteroides vulgatus.

[0014] Therefore, in one aspect, the present invention provides the use of Bacteroides monomorpha and / or Bacteroides vulgaris in the preparation of formulations for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject.

[0015] In a second aspect, the present invention provides an formulation for treating and / or preventing coronary artery disease in a subject, or for lowering blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, comprising an effective amount of Bacteroides monomorpha and / or Bacteroides commonis.

[0016] In a third aspect, the present invention provides a method for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, comprising the step of administering an effective amount of Bacteroides monomorpha and / or Bacteroides commonis to a subject in need of such treatment.

[0017] In a fourth aspect, the present invention provides methods for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject. Brief description of the attached diagram

[0019] These and other aspects and advantages of the invention will become clear and more readily understood from the following description taken in conjunction with the accompanying drawings, wherein:

[0020] Figure 1 : 65 of the most discriminative MLG species in a random forest model based on 126 MLG markers. Importance of the bar length indicator variable (MLG species).

[0021] Figure 2: Effect of application of Bacteroides strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides var. ATCC 8482, Bacteroides var. PC510 or Bacteroides var. mpk) on OGTT curves under cholesterol-rich HF diet conditions. Figure 2A Results obtained before application of Bacteroides strains (at week 16); Figure 2BResults obtained after administration of Bacteroides strains (at week 24). At week 16, no significant differences in blood glucose levels were observed in any of the HF-fed groups. Figure 2A However, after 8 weeks of tube feeding (week 24), the AUC (area under the curve) of blood glucose (mmol / L) was significantly lower in both the *Bacteroides monomorpha* group and the *Bacteroides var. congenita* group compared to the AS group. Figure 2B ).

[0022] Figure 3 Quantitative results of coronary atherosclerotic lesion area in mice after administration of Bacteroides strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT7771, Bacteroides monomorpha 0061, Bacteroides commonis ATCC 8482, Bacteroides commonis PC510, or Bacteroides commonis mpk) (n=8 / group). Values ​​are shown as mean ± SEM. According to analysis of variance and subsequent Tukey post-hoc test (p>0.05), the differences in values ​​between groups with the same letter label were not statistically significant. Figure 3 As shown, the analysis of atherosclerotic lesions revealed no significant differences among mice treated with different Bacteroides strains for 8 weeks. In contrast, the mean coronary atherosclerotic lesion area was significantly reduced in the six groups treated with Bacteroides strains compared to the AS group.

[0023] Figure 4 Histological characteristics of atherosclerotic lesions in the aortic root (stained with Oil Red O). A: NC group; BD: Bacteroides monomorpha group (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, and Bacteroides monomorpha 0061, respectively); EG: Bacteroides commonis group (Bacteroides commonis ATCC 8482, Bacteroides commonis PC510, and Bacteroides commonis mpk, respectively); H: AS group. Results showed that compared with the healthy control group ( Figure 4 Compared to groups A and NC, at week 24, mice in the AS group fed a cholesterol-rich HF diet and a placebo developed lipid-rich atherosclerotic lesions at the aortic root. Figure 4 H, AS group); however, compared with the AS group, mice treated with Bacteroides strains for 8 weeks showed a significant reduction in foam cells and lipid deposition in the subendothelial region (H, AS group); Figure 4 B~4G).

[0024] Figure 5Characterization of the components of atherosclerotic lesions by staining neutral lipids with Oil Red O. Values ​​are shown as mean ± SEM. According to analysis of variance and subsequent Tukey post-hoc test (p>0.05), there were no statistically significant differences in values ​​between groups with the same letter label. Results showed that, compared with the AS group, Bacteroides treatment significantly reduced lipid accumulation in mice, indicating that Bacteroides treatment promoted cholesterol efflux from diseased macrophages and inhibited the development of atherosclerosis.

[0025] Detailed Explanation

[0026] The terms used herein have the meanings commonly understood by one of ordinary skill in the art. However, for a better understanding of the invention, definitions and explanations of the relevant terms are provided below.

[0027] According to the present invention, the term "coronary artery disease (CAD)" is also known as atherosclerotic heart disease, atherosclerotic cardiovascular disease, coronary artery disease, or ischemic heart disease (IHD), and is the most common type of heart disease and cause of heart attacks. This disease is caused by plaque buildup along the inner walls of the coronary arteries, which narrows the arteries and reduces blood flow to the heart.

[0028] According to the present invention, the term "prevent" (preventing or prevention) refers to preventing, inhibiting or delaying the occurrence of diseases (such as CAD).

[0029] According to the present invention, the term "treatment" (treat, treating, or treatment) refers to treating or curing a disease (such as CAD), delaying the onset of symptoms of a disease (such as CAD), and / or delaying the progression of a disease (such as CAD).

[0030] According to the present invention, the term "effective amount" refers to an amount that can effectively achieve the intended purpose. For example, a preventive effective amount may be an amount that is effective or sufficient to prevent, inhibit, or delay the onset of a disease (such as CAD); a therapeutic effective amount may be an amount that is effective or sufficient to treat or cure a disease (such as CAD), delay the onset of symptoms of a disease (such as CAD), and / or delay the progression of a disease (such as CAD). Such an effective amount can be readily determined by those skilled in the art or by a physician and may be related to the intended purpose (prevention or treatment), the general health condition of the subject, age, sex, weight, severity of the disease to be treated, complications, routine administration, etc. The determination of such an effective amount is entirely within the capabilities of those skilled in the art.

[0031] Terms such as “a,” “an,” and “the” are intended not only to refer to a singular entity but also to include a kind that may be illustrated by specific examples. Unless indicated in the claims, the terminology herein is used to describe specific embodiments of the invention but is not intended to limit the invention.

[0032] In one aspect, the present invention provides the use of Bacteroides uniformis and / or Bacteroides vulgatus in the preparation of formulations for treating and / or preventing coronary artery disease in a subject, or for lowering blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject.

[0033] In a preferred embodiment, the formulation may comprise any strain of Bacteroides monomorphosum or any combination thereof. For example, the formulation may comprise one or more strains of Bacteroides monomorphosum, such as at least 2, 3, 4, 5 or more strains. In a preferred embodiment, the Bacteroides monomorphosum is selected from Bacteroides monomorphosum ATCC 8492, Bacteroides monomorphosum CECT 7771, Bacteroides monomorphosum 0061 and any combination thereof.

[0034] In a preferred embodiment, the formulation may comprise any strain of *Bacteroides commonis* or any combination thereof. For example, the formulation may comprise one or more strains of *Bacteroides commonis*, such as at least 2, 3, 4, 5 or more strains. In a preferred embodiment, *Bacteroides commonis* is selected from *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, and any combination thereof.

[0035] In a preferred embodiment, *Bacteroides monomorpha* and *Bacteroides vulgaris* as described above can be used in combination. Therefore, the formulation may comprise one or more strains of *Bacteroides monomorpha* and one or more strains of *Bacteroides vulgaris*.

[0036] In a preferred embodiment, the formulation is a pharmaceutical composition. Such a pharmaceutical composition may contain a therapeutically or preventively effective amount of Bacteroides monomorphosum and / or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical field. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, or granules.

[0037] In a preferred embodiment, the formulation is a nutritional pharmaceutical composition or a food composition. Such a composition may be in solid, semi-solid, or liquid form. In a preferred embodiment, the formulation is a dairy product, such as milk, milk powder, or yogurt.

[0038] In a preferred embodiment, the formulation further comprises an additional agent for treating and / or preventing coronary artery disease, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions. This additional agent may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium channel blockers, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

[0039] Additionally, when the formulation contains *Bacteroides monomorpha*, the additional agent may contain any strain of *Bacteroides commonis*, such as *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, or any combination thereof. Similarly, when the formulation contains *Bacteroides commonis*, the additional agent may include any strain of *Bacteroides monomorpha*, such as *Bacteroides monomorpha* ATCC 8492, *Bacteroides monomorpha* CECT 7771, *Bacteroides monomorpha* 0061, or any combination thereof.

[0040] In a preferred embodiment, the formulation comprises a unit dose of Bacteroides monomorpha and / or Bacteroides commonis, for example, at a concentration of at least 1 x 10⁻⁶. 6 cfu / g, such as at least 1x10 7 cfu / g, at least 1x10 8 cfu / g, at least 1x10 9 cfu / g, at least 1x10 10 cfu / g, at least 1x10 11 cfu / g or at least 1x10 12 CFU / g of Bacteroides monomorpha and / or Bacteroides commonis. When the formulation is in liquid form (e.g., solution, suspension, emulsion), it may contain a concentration of at least 1 x 10⁻⁶. 6 cfu / ml, such as at least 1x10 7 cfu / ml, at least 1x10 8 cfu / ml, at least 1x10 9 cfu / ml, at least 1x10 10 cfu / ml, at least 1x10 11 cfu / ml or at least 1x10 12 CFU / ml of Bacteroides monomorphosum and / or Bacteroides var. ...

[0041] In a preferred embodiment, the preparation may be administered in conjunction with an additional therapy. This additional therapy may be any therapy known for coronary artery disease, such as coronary interventional procedures (e.g., angioplasty) and coronary artery bypass grafting.

[0042] In a preferred embodiment, the subject is a mammal, such as a human.

[0043] In a second aspect, the present invention provides an preparation for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, comprising an effective amount of Bacteroides monomorpha and / or Bacteroides commonis.

[0044] In a preferred embodiment, the formulation may comprise any strain of Bacteroides monomorphosum or any combination thereof. For example, the formulation may comprise one or more strains of Bacteroides monomorphosum, such as at least 2, 3, 4, 5 or more strains. In a preferred embodiment, the Bacteroides monomorphosum is selected from Bacteroides monomorphosum ATCC 8492, Bacteroides monomorphosum CECT 7771, Bacteroides monomorphosum 0061 and any combination thereof.

[0045] In a preferred embodiment, the formulation may comprise any strain of *Bacteroides commonis* or any combination thereof. For example, the formulation may comprise one or more strains of *Bacteroides commonis*, such as at least 2, 3, 4, 5 or more strains. In a preferred embodiment, *Bacteroides commonis* is selected from *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, and any combination thereof.

[0046] In a preferred embodiment, *Bacteroides monomorpha* and *Bacteroides vulgaris* as described above can be used in combination. Therefore, the formulation may comprise one or more strains of *Bacteroides monomorpha* and one or more strains of *Bacteroides vulgaris*.

[0047] In a preferred embodiment, the formulation is a pharmaceutical composition. Such a pharmaceutical composition may contain a therapeutically or preventively effective amount of Bacteroides monomorphosum and / or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical field. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, or granules.

[0048] In a preferred embodiment, the formulation is a nutritional pharmaceutical composition or a food composition. Such a composition may be in solid, semi-solid, or liquid form. In a preferred embodiment, the formulation is a dairy product, such as milk, milk powder, or yogurt.

[0049] In a preferred embodiment, the formulation further comprises an additional agent for treating and / or preventing coronary artery disease, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions. This additional agent may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium channel blockers, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

[0050] Additionally, when the formulation contains *Bacteroides monomorpha*, the additional agent may contain any strain of *Bacteroides commonis*, such as *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, or any combination thereof. Similarly, when the formulation contains *Bacteroides commonis*, the additional agent may include any strain of *Bacteroides monomorpha*, such as *Bacteroides monomorpha* ATCC 8492, *Bacteroides monomorpha* CECT 7771, *Bacteroides monomorpha* 0061, or any combination thereof.

[0051] In a preferred embodiment, the formulation comprises a unit dose of Bacteroides monomorpha and / or Bacteroides commonis, for example, at a concentration of at least 1 x 10⁻⁶. 6 cfu / g, such as at least 1x10 7 cfu / g, at least 1x10 8 cfu / g, at least 1x10 9 cfu / g, at least 1x10 10 cfu / g, at least 1x10 11 cfu / g or at least 1x10 12 CFU / g of Bacteroides monomorpha and / or Bacteroides commonis. When the formulation is in liquid form (e.g., solution, suspension, emulsion), it may contain a concentration of at least 1 x 10⁻⁶. 6 cfu / ml, such as at least 1x10 7 cfu / ml, at least 1x10 8 cfu / ml, at least 1x10 9 cfu / ml, at least 1x10 10 cfu / ml, at least 1x10 11 cfu / ml or at least 1x10 12 CFU / ml of Bacteroides monomorphosum and / or Bacteroides var. ...

[0052] In a preferred embodiment, the preparation may be administered in conjunction with an additional therapy. This additional therapy may be any therapy known for coronary artery disease, such as coronary interventional procedures (e.g., angioplasty) and coronary artery bypass grafting.

[0053] In a preferred embodiment, the subject is a mammal, such as a human.

[0054] In a third aspect, the present invention provides a method for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, comprising the step of administering an effective amount of Bacteroides monomorpha and / or Bacteroides commonis to a subject in need of such treatment.

[0055] In a preferred embodiment, any strain of Bacteroides monomorphosum or any combination thereof may be administered to the subject. For example, one or more strains of Bacteroides monomorphosum, such as at least 2, 3, 4, 5 or more strains, may be administered to the subject. In a preferred embodiment, Bacteroides monomorphosum is selected from Bacteroides monomorphosum ATCC 8492, Bacteroides monomorphosum CECT 7771, Bacteroides monomorphosum 0061 and any combination thereof.

[0056] In a preferred embodiment, any strain of *Bacteroides commonis* or any combination thereof may be administered to the subject. For example, one or more strains of *Bacteroides commonis*, such as at least 2, 3, 4, 5 or more strains, may be administered to the subject. In a preferred embodiment, *Bacteroides commonis* is selected from *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, and any combination thereof.

[0057] In a preferred embodiment, Bacteroides monomorphosum and Bacteroides vulgaris, as described above, can be used in combination. Therefore, one or more strains of Bacteroides monomorphosum and one or more strains of Bacteroides vulgaris can be administered to the subject.

[0058] In a preferred embodiment, *Bacteroides monomorphosum* and / or *Bacteroides vulgaris* can be formulated and administered as a pharmaceutical composition. Such a pharmaceutical composition may contain a therapeutically or preventively effective amount of *Bacteroides monomorphosum* and / or *Bacteroides vulgaris*. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical field. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, or granules.

[0059] In a preferred embodiment, *Bacteroides monomorpha* and / or *Bacteroides vulgaris* can be formulated and administered as a nutritional pharmaceutical composition or a food composition. Such compositions can be in solid, semi-solid, or liquid form. In a preferred embodiment, such compositions are dairy products, such as milk, milk powder, or yogurt.

[0060] In a preferred embodiment, the method further includes administering additional agents for treating and / or preventing coronary artery disease, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions. These additional agents may be administered before, simultaneously with, or after the administration of *Bacteroides monomorpha* and / or *Bacteroides vulgaris*.

[0061] In a preferred embodiment, this additional agent may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium channel blockers, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

[0062] Additionally, when administering *Bacteroides monomorpha* to a subject, the additional agent may include any strain of *Bacteroides commonis*, such as *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, or any combination thereof. Similarly, when administering *Bacteroides commonis* to a subject, the additional agent may include any strain of *Bacteroides monomorpha*, such as *Bacteroides monomorpha* ATCC 8492, *Bacteroides monomorpha* CECT 7771, *Bacteroides monomorpha* 0061, or any combination thereof.

[0063] In a preferred embodiment, it can be at least 1x10 5 cfu / kg, such as at least 1x10 6 cfu / kg, at least 1x10 7 cfu / kg, at least 1x10 8 cfu / kg, at least 1x10 9 cfu / kg, at least 1x10 10 cfu / kg, at least 1x10 11 cfu / kg or at least 1x10 12 Bacteroides monomorphosum and / or Bacteroides commonis are administered at a dose of cfu / kg of the subject's body weight. In a preferred embodiment, Bacteroides monomorphosum and / or Bacteroides commonis can be administered three times daily, twice daily, once daily, once every two days, or once weekly.

[0064] In a preferred embodiment, the method further includes administering additional therapy. This additional therapy can be any therapy known for coronary artery disease, such as coronary interventional procedures (e.g., angioplasty) and coronary artery bypass grafting.

[0065] In a preferred embodiment, the subject is a mammal, such as a human.

[0066] In a fourth aspect, the present invention provides methods for treating and / or preventing coronary artery disease in a subject, or for reducing blood glucose or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject.

[0067] In a preferred embodiment, any strain of *Bacteroides monomorphosus* or any combination thereof may be used in the method. For example, one or more strains of *Bacteroides monomorphosus*, such as at least two, three, four, five or more strains, may be used in the method. In a preferred embodiment, *Bacteroides monomorphosus* is selected from *Bacteroides monomorphosus* ATCC 8492, *Bacteroides monomorphosus* CECT 7771, *Bacteroides monomorphosus* 0061, and any combination thereof.

[0068] In a preferred embodiment, any strain of *Bacteroides commonis* or any combination thereof may be used in the method. For example, one or more strains of *Bacteroides commonis*, such as at least two, three, four, five or more strains, may be used in the method. In a preferred embodiment, *Bacteroides commonis* is selected from *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, and any combination thereof.

[0069] In a preferred embodiment, *Bacteroides monomorphosum* and *Bacteroides vulgaris* as described above can be used in combination. Therefore, one or more strains of *Bacteroides monomorphosum* and one or more strains of *Bacteroides vulgaris* can be used in this method.

[0070] In a preferred embodiment, *Bacteroides monomorphosum* and / or *Bacteroides vulgaris* can be formulated and administered as a pharmaceutical composition. Such a pharmaceutical composition may contain a therapeutically or preventively effective amount of *Bacteroides monomorphosum* and / or *Bacteroides vulgaris*. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical field. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, or granules.

[0071] In a preferred embodiment, *Bacteroides monomorpha* and / or *Bacteroides vulgaris* can be formulated and administered as a nutritional pharmaceutical composition or a food composition. Such compositions can be in solid, semi-solid, or liquid form. In a preferred embodiment, such compositions are dairy products, such as milk, milk powder, or yogurt.

[0072] In a preferred embodiment, *Bacteroides monomorphosum* and / or *Bacteroides vulgaris* may be administered in combination with additional agents for the treatment and / or prevention of coronary artery disease, or for lowering blood glucose or lipid levels, or for improving coronary atherosclerotic lesions. These additional agents may be administered before, simultaneously with, or after the administration of *Bacteroides monomorphosum* and / or *Bacteroides vulgaris*.

[0073] In a preferred embodiment, this additional agent may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium channel blockers, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

[0074] Additionally, when administering *Bacteroides monomorpha* to a subject, the additional agent may include any strain of *Bacteroides commonis*, such as *Bacteroides commonis* ATCC 8482, *Bacteroides commonis* PC510, *Bacteroides commonis* mpk, or any combination thereof. Similarly, when administering *Bacteroides commonis* to a subject, the additional agent may include any strain of *Bacteroides monomorpha*, such as *Bacteroides monomorpha* ATCC 8492, *Bacteroides monomorpha* CECT 7771, *Bacteroides monomorpha* 0061, or any combination thereof.

[0075] In a preferred embodiment, *Bacteroides monomorpha* and / or *Bacteroides vulgaris* can be distributed at a rate of at least 1 x 10⁻⁶. 5 cfu / kg, such as at least 1x10 6 cfu / kg, at least 1x10 7 cfu / kg, at least 1x10 8 cfu / kg, at least 1x10 9 cfu / kg, at least 1x10 10 cfu / kg, at least 1x10 11 cfu / kg or at least 1x10 12 The dosage is cfu / kg of the subject's body weight. In a preferred embodiment, Bacteroides monomorpha and / or Bacteroides vulgaris can be administered three times daily, twice daily, once daily, once every two days, or once weekly.

[0076] In a preferred embodiment, *Bacteroides monomorpha* and / or *Bacteroides vulgaris* may be administered in conjunction with additional therapy. This additional therapy may be any therapy known for coronary artery disease, such as coronary interventions (e.g., angioplasty) and coronary artery bypass grafting.

[0077] In a preferred embodiment, the subject is a mammal, such as a human.

[0078] The invention is further illustrated by the following non-limiting examples. Unless otherwise stated, parts and percentages are by weight, and degrees are in degrees Celsius. All reagents used are commercially available. It will be apparent to those skilled in the art that these examples, while indicating preferred embodiments of the invention, are given by way of illustration only. Example

[0079] Example 1: Identification of biomarkers associated with coronary artery disease risk

[0080] 1.1: Sample Collection

[0081] In 2011, Guangdong Provincial People's Hospital collected stool samples from 165 subjects in southern China, including 88 patients with atherosclerotic cardiovascular disease (ACVD) and 77 control subjects (training group, Table 1). ACVD patients were diagnosed and classified according to pathological characteristics. Subjects were asked to collect fresh stool samples at the hospital. Collected samples were placed in sterile tubes and immediately stored at -80°C until further analysis.

[0082] This study has received full ethical approval, and all patients provided written informed consent. The study was approved by the Institutional Review Committee of Guangdong Provincial General Hospital.

[0083] Table 1: Baseline characteristics of ACVD patients and control subjects. The fourth column reports the results of the Wilcoxon rank-sum test.

[0084]

[0085] Note: For information on gender, the gender of one of the 88 patients and two of the 77 control subjects was unknown.

[0086] 1.2: DNA Extraction

[0087] Fecal samples were thawed on ice and DNA was extracted using the Qiagen QIAamp DNA Stool Mini Kit (Qiagen) according to the manufacturer's instructions. The extract was treated with RNase-free DNase to remove RNA contamination. The amount of DNA was determined using a NanoDrop spectrophotometer, a Qubit fluorometer (with the Quant-iT™ dsDNA BR Assay Kit), and gel electrophoresis.

[0088] 1.3: DNA Library Construction and Sequencing

[0089] DNA libraries were constructed according to the manufacturer's instructions (Illumina). The inventors used standard workflows for DNA clustering, template hybridization, isothermal amplification, single-stranding, blocking and denaturation, and hybridization with sequencing primers. The inventors constructed a paired-end (PE) sequencing library, in which each sample contained an insert fragment of 350 bp, followed by high-throughput sequencing to obtain approximately 30 million PE reads of 2 × 100 bp in length. High-quality reads were obtained by filtering from the raw Illumina reads to remove low-quality reads with indeterminate 'N' bases, adapter contamination, and human DNA contamination, and by simultaneously trimming low-quality end bases from the reads.

[0090] The inventors output approximately 4.77 Gb of fecal microbiota sequencing data (high-quality, valid data) for each of 165 samples (88 patients and 77 control subjects) on the Illumina HiSeq 2000 platform (Table 2).

[0091] Table 2: Overview of metagenomic data. The fourth column reports the results of the Wilcoxon rank-sum test.

[0092]

[0093] 1.4: Processing and Analysis of Metagenomic Data

[0094] 1.4.1: Gene Catalog Construction

[0095] Gene catalog construction. Using the same parameters used to construct the gene catalog for type 2 diabetes (Qin, J. et al. Ametagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55-60 (2012), incorporated herein by reference), the inventors used SOAPdenovo v1.06 (Li, R. et al. De novoassembly of human genomes with massively parallel short readsequencing. Genome Research 20, 265-272, doi:10.1101 / gr.097261.109 (2009), incorporated herein by reference) and GeneMark v2.7 (Zhu, W., Lomsadze, A. & Borodovsky, M. Ab initio gene identification in metagenomic sequences. Nucleic acids research). 38, e132, doi:10.1093 / nar / gkq275 (2010), incorporated herein by reference) performed de novo assembly and gene prediction on high-quality reads from 165 samples. All predicted genes were paired using BLAT, and such genes were removed as redundancy. Genes whose sequences exceeding 90% of their length showed greater than 95% identity (no gaps allowed) when aligned with another gene were obtained, resulting in a non-redundant gene catalog containing 4,537,046 genes (4.5M gene catalog).

[0096] Taxonomic assignment of genes. The taxonomic assignment of genes is predicted using the internal process described in the published T2D paper (Qin et al., 2012, ibid.).

[0097] 1.4.2: Constructing the Data Profile

[0098] Gene profile. A gene profile for association studies was constructed using the 4,537,046 genes mentioned above and their relative abundance in 165 samples. (The inventors used the same method as described in the published T2D paper (Qin et al. 2012, ibid.) to calculate the relative gene abundance.)

[0099] IMG and mOTU species profiles were used. Total valid fecal reads were compared with 4,653 reference genomes from IMG v400 (Markowitz, VM et al., IMG: the integrated microbial genomes database and comparative analysis system. Nucleic acids research 40, D115-D122 (2012), incorporated herein by reference) and 79,268 sequences from mOTU references (Sunagawa, S. et al., Metagenomic species profiling using universal phylogenetic marker genes. Nature methods 10, 1196-1199 (2013), incorporated herein by reference). 1290 IMG species (species shared in at least 10 subjects) and 560 mOTU species were identified.

[0100] 1.4.3: Analysis of Factors Affecting the Gut Microbiota Genome Profile. The inventors used permutational multivariate analysis of variance (PERMANOVA) to assess the impact of 25 different characteristics (including CAD status, HDLC, CHOL, sex, FBG, hypertension, APOB, age, CREA, LDLC, HbA1c, APOA, TP, diabetes, ALB, TRIG, BMI, WHR, Lpa, HBDH, CKMB, AST, CK, ProBNP_E_, and ALT) on the genome profile of a 4.5M reference gene catalog. The inventors used the method implemented in the "vegan" software package in R, and obtained the p-values ​​of the permutations through 10,000 permutations. The inventors also used the "p.adjust" function in R and the Benjamini-Hochberg method to correct for multiple tests to obtain q-values ​​for each test. PERMANOA identified two important factors associated with the gut microbiota (based on genome profile) (q < 0.05, Table 3). Analysis showed that CAD and HDLC status were the most significantly associated biomarkers, indicating that disease status is a major determinant of gut microbiota composition. Sex, age, and some clinical indicators of CAD, such as CHOL, FGB, hypertension, and APOB, were also important factors.

[0101] Table 3: PermanoVA based on Euclidean distance analysis of gene profiles. This analysis was used to examine whether clinical parameters and ACVD status have a significant impact on the gut microbiota (i.e., q value < 0.05).

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[0103] 1.4.4: Identification of ACVD-related biomarkers

[0104] Identification of ACVD-related genes. To identify the association between metagenomic profiles and ACVD, a two-tailed Wilcoxon rank-sum test was performed on the 2.1M high-incidence gene profile (genes present in fewer than 10 samples out of all 165 samples were removed). A total of 438,750 gene markers (representing 20.48% of the 2.1M genes) were obtained, which were enriched in both patient and control subjects (p < 0.01, FDR = 2.23%).

[0105] Estimating the false discovery rate (FDR). The inventors applied the "q-value" method proposed in previous research (Storey, JDA direct approach to false discovery rates. Journal of the Royal Statistical Society 64, 479-498 (2002), incorporated herein by reference) instead of the sequential p-value rejection method to estimate the FDR.

[0106] Receiver Operating Characteristic (ROC) Analysis. The inventors applied ROC analysis to evaluate the performance of ACVD classification based on metagenomic biomarkers. The inventors then used the "pROC" package in R software to plot ROC curves.

[0107] 1.4.5: Construction of MLG species and identification of ACVD-related MLG species markers

[0108] 126 MLG species based on gene profiles of 438,750 ACVD-related markers. The inventors constructed metagenomic linkage groups (MLGs) using 438,750 gene markers, employing the same method described in the published T2D paper (Qin et al., 2012, ibid.). All 438,750 genes were annotated by aligning these genes to 4,653 reference genomes in IMG v400. If more than 50% of the constitutive genes in an MLG were annotated to a genome, that MLG was assigned to that genome; otherwise, it was designated unclassified. A total of 136 MLG genomes with more than 550 genes were selected. MLG genomes belonging to the same species were grouped to construct MLG species. Ultimately, the inventors obtained 127 MLG species. The inventors used the Benjamini-Hochberg adjustment method to perform a Wilcoxon rank-sum test on 127 MLG species, of which 126 MLGs were selected as ACVD-related MLGs, q < 0.05. To estimate the relative abundance of an MLG species, the inventors estimated the mean abundance of genes in that MLG species after removing the 5% lowest and 5% highest abundance genes (Qin et al., 2012, ibid.).

[0109] The inventors constructed a total of 136 metagenomic linkage groups (MLGs with >550 genes) based on the distribution and occurrence of 438,750 genes (Qin et al., 2012, ibid.). The MLGs included 94.8% of the significant genes (P-value <0.01). The 136 MLGs (each with >550 genes, >50% coverage, and q <0.05) were annotated in the NCBI database, and MLGs from the same species were grouped together to obtain 126 MLG species.

[0110] Identification of MLG species markers. To identify MLG species markers, the inventors analyzed 126 ACVD-related MLG species using the "randomForest 4.5-36" package in R software version 2.10. First, the inventors ranked all 126 MLG species based on importance given by the "randomForest" method (Liaw, Andy & Wiener, Matthew. Classification and Regression by randomForest, R News (2002), Vol. 2 / 3, p. 18, incorporated herein by reference). MLG marker sets were constructed by creating incremental subsets of the top-ranked MLG species, starting with 5 MLG species and ending with all 126 MLG species. For each MLG marker set, the inventors calculated the false prediction rate in a cohort of 165 individuals. Finally, the MLG marker set with the lowest false prediction rate (comprising 65 MLG species) was selected as the MLG species marker set. Figure 1 The false negative (FN) rate was 6.8%, and the false positive (FP) rate was 3.89%. Furthermore, the inventors plotted ROC curves based on the selected MLG species biomarkers using out-of-bag (OOB) disease prediction probabilities from the randomForest model, and calculated the area under the ROC curve to be 98.17% using the R package "pROC".

[0111] Among the 65 MLG species, the MLG species enriched in the control group, Bacteroides monomorpha (q=4.21E-11) and Bacteroides vulgaris (q=1.80E-09), were designated as SCFA-producing bacteria.

[0112] 1.4.6: Identification of ACVD-Related IMG and mOTU Species. IMG and mOTU species markers were identified based on the IMG and mOTU species profiles. The inventors identified ACVD-related IMG and mOTU species (q < 0.05) using the Wilcoxon rank-sum test with Benjamini-Hochberg adjustment. Subsequently, the randomForest method (as in the selection of MLG species markers) was used to select IMG and mOTU species markers.

[0113] Based on Wilcoxon rank-sum test and random forest selection, 65 IMG species with an ROC of 98.52% and 15 mOTU species with an ROC of 96.16% also clearly distinguished CAD patients from healthy subjects (q<0.05; see Tables 5 and 6). Similar to the 65 MLG species markers, the inventors found significant enrichment of *Bacteroides monomorpha* in the control group among the 65 IMG species markers and the 15 mOTU species markers.

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[0124] Example 2: Validation in CAD-related animal experiments

[0125] To verify the ability of probiotics Bacteroides monomorphosum and Bacteroides vulgaris to prevent and treat CAD-related diseases, the inventors conducted animal experiments.

[0126] 2.1: Method

[0127] To investigate the inhibitory effects of Bacteroides monomorphosum and Bacteroides vulgaris on the aortic plaque area of ​​atherosclerotic mice, mice were fed a high-fat diet for 16 weeks to establish an atherosclerosis model. Then, from week 16, mice were given Bacteroides monomorphosum and Bacteroides vulgaris, and the effects on blood glucose, OGTT (oral glucose tolerance test), blood lipids, and atherosclerotic plaque area were observed.

[0128] 2.1.1: Animals and Treatment

[0129] Sixty-four male specific pathogen-free (SPF) C57BL / 6J mice (10 weeks old, weighing 22.5–25.9 g) were purchased from the Laboratory Animal Center of Southern Medical University, China. Mice used in the study of diet-induced atherosclerosis were given free access to drinking water and food for two weeks to acclimatize. They were then randomly divided into two groups: one group (8 mice) was fed a normal diet (NC group, 10% of calories from fat and 3.85 total kcal per gram, purchased from Research Diets, Inc., New Brunswick, NJ, USA) as a healthy control. The other group (56 mice) was fed a high-fat diet with 2% cholesterol (60% of calories from fat and 5.24 total kcal per gram, purchased from Research Diets, Inc.) to induce atherosclerosis. After 16 weeks, these 56 mice were randomly divided into seven groups (8 mice per group). One group served as the atherosclerosis control group (AS group), receiving the same cholesterol-rich high-frequency (HF) diet as described above, and receiving 200 μl of Columbia blood culture medium (DSMZ Medium 693) as a placebo. The other six groups (B1–B6) also received a cholesterol-rich HF diet, and each group of mice was administered 200 μl via tube feeding of a bacterial suspension containing one of six candidate probiotic strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, and Bacteroides vulgaris mpk) suspended in Columbia blood culture medium at a concentration of 10%. 9 -10 10 cfu / ml (freshly prepared weekly). The mice were then fed for another 8 weeks.

[0130] Bacteroides monomorpha ATCC 8492 and Bacteroides spp. ATCC 8482 were purchased from the American Type Culture Collection (ATCC).

[0131] Bacteroides monomorpha CECT 7771 was purchased from the Spanish General Microbiological Collection Center.

[0132] Bacteroides uniformis 0061 was obtained from the Virginia Tech Anaerobic Bacteria Laboratory Culture Collection (Shoemaker, NB, & Salyers, AA (1988). Tetracycline-dependent appearance of plasmid-like forms in Bacteroides uniformis 0061 mediated by conjugal Bacteroides tetracycline resistance elements. Journal of Bacteriology, 170(4), 1651-1657).

[0133] Bacteroides vulgatus PC510 was obtained from the CSIRO Preventive Health Flagship Research Program and the Livestock Industry Sector (Páraic O Cuív et al. Draft genome sequence of Bacteroides vulgatus PC510, a strain isolated from human feces. Journal of bacteriology, 2011, 193(15):4025-6).

[0134] Bacteroides vulgatus mpk was obtained from the Institute of Medical Microbiology and Hygiene, University of Tübingen (Waidmann M et al. Bacteroides vulgatus protects against Escherichia coli-induced colitis ingnotobiotic interleukin-2-deficient mice. Gastroenterology. 2003 Jul; 125(1):162-77).

[0135] The strain was purified and cultured using anaerobic culture techniques. The composition of the Columbia blood culture medium used for culture is described in DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, German Collection of Microorganisms and Cell Cultures) Medium 693. For experimental purposes, the strain was anaerobically propagated at 37°C for 48 hours.

[0136] 2.1.2: Oral Glucose Tolerance Test (OGTT)

[0137] After an 8-hour fast, mice were orally administered glucose at a dose of 2.0 g / kg body weight. Blood samples were collected from the tail before and at 15, 30, 60, and 120 minutes after glucose administration, and blood glucose levels were measured using a glucometer (Roche Diagnostics, Mannheim, Germany). The blood glucose level before glucose administration represents the fasting blood glucose level.

[0138] 2.1.3: Collection of Blood and Aorta

[0139] At the end of week 24, after a 12-hour fast, all blood was collected from the orbital vascular plexus. Serum was obtained by centrifugation at 5000 rpm for 15 minutes at 4°C and stored at -80°C for subsequent biochemical assays. All animals were euthanized by cervical dislocation. Plasma triglycerides (TG) and total cholesterol (TC) were measured using a kit combining enzymatic reactions and spectrophotometric detection of final plasma products (Nanjing Jiancheng Bio-engineering Institute, China). Aorta was collected and processed for cross-sectional analysis of plaque area in the aortic root.

[0140] 2.1.4: Assessment of Atherosclerotic Plaques

[0141] After blood collection, heparin was injected into the inferior vena cava, and the aorta was extracted from the aortic root under a microscope, fixed in paraformaldehyde, embedded in 10% phosphate-buffered formalin, and cut into 6 μm thick sections. Optical microscopy was performed to evaluate changes in atherosclerosis. Tissue sections on slides were scanned to generate virtual slides for quantitative assessment using iVision software (BioVision Technologies, Exton, PA, USA). To detect neutral lipids, tissue sections were stained with Oil Red O. After capturing images of the sections, the red area was determined over the total section area using computer-aided color-gated measurements (SigmaScanPro 5; SPSS Inc., Chicago, IL, USA).

[0142] 2.2: Results

[0143] 2.2.1: Effects on blood glucose and OGTT

[0144] At week 16, no significant differences in blood glucose levels were observed in all HF feeding groups. Figure 2A However, after 8 weeks of tube feeding (week 24), compared with the AS group, the AUC (area under the curve) of blood glucose (mmol / L) was significantly lower in both the *Bacteroides monomorpha* group and the *Bacteroides var. congenita* group in the oral glucose tolerance test. Figure 2BThe AUC data for each group are shown in Table 7.

[0145] Table 7: AUC values ​​of the OGTT curves for each group. Each value is shown as mean ± SEM. According to ANOVA and subsequent Tukey post-hoc tests, the differences between values ​​in groups labeled with the same letter were not statistically significant. Between groups, the same letter labeling indicated no significant difference in values ​​between the labeled groups as determined by Tukey's test (p>0.05).

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[0147] 2.2.2: Effects on serum lipids

[0148] The effects of administration of *Bacteroides monomorpha* ATCC 8492, CECT 7771, and 0061, and *Bacteroides commonis* ATCC 8482, PC510, and mpk on serum lipids are shown in Table 8. Compared with the NC group, the treatment of a cholesterol-rich HF diet with tube feeding of a placebo significantly increased plasma triglycerides and total plasma cholesterol. However, compared with the AS group, serum lipid levels were significantly lower in the *Bacteroides monomorpha* and *Bacteroides commonis* tube feeding groups.

[0149] Table 8: Effects of Bacteroides strain application on plasma triglycerides (TG) and total cholesterol (TC). Each value is shown as mean ± SEM. According to ANOVA and subsequent Tukey post-hoc test, there were no statistically significant differences between groups labeled with the same letter. Among the groups, the same letter labeling indicated no significant difference in values ​​between the labeled groups, as determined by Tukey's test (p>0.05).

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[0151] 2.2.3: Efficacy of Bacteroides strains in treating coronary atherosclerotic lesions in mice.

[0152] Figure 3 This study presents quantitative results of the area of ​​coronary atherosclerotic lesions in mice after administration of Bacteroides strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides commonis ATCC 8482, Bacteroides commonis PC510, or Bacteroides commonis mpk) (n = 8 / group). Values ​​are shown as mean ± SEM. According to analysis of variance and subsequent Tukey post-hoc test (p > 0.05), there were no statistically significant differences between groups with the same letter designation.

[0153] like Figure 3As shown, the analysis of atherosclerotic lesions indicated no significant differences among mice treated with different Bacteroides strains for 8 weeks. In contrast, compared with the AS group, the mean coronary atherosclerotic lesion area was significantly reduced in the six groups treated with Bacteroides strains. Figure 3 (Table 9).

[0154] As shown by the histological features of the longitudinal section of the aortic root, compared with the healthy control group ( Figure 4 Compared to groups A and NC, mice in the AS group, after being fed a cholesterol-rich HF diet and a placebo, developed lipid-rich atherosclerotic lesions in the aortic root at week 24. Figure 4 H, AS group). In contrast, mice treated with Bacteroides strains for 8 weeks showed a significant reduction in foam cells and lipid deposition in the subendothelial region compared to the AS group. Figure 4 B~4G).

[0155] Differences in lipid accumulation indicated that *Bacteroides monomorphosum* ATCC 8492, *Bacteroides monomorphosum* CECT7771, *Bacteroides monomorphosum* 0061, *Bacteroides var. mongolicum* ATCC 8482, *Bacteroides var. mongolicum* PC510, and *Bacteroides var. mongolicum* mpk alleviated the development of atherosclerosis in a mouse model induced by a cholesterol-rich high-fat diet. Compared with the AS group, quantitative detection of lipid accumulation in atherosclerotic lesions by Oil Red O staining showed that lipid accumulation was significantly reduced in mice treated with *Bacteroides*. Figure 5 (Table 9). These results indicate that Bacteroides treatment promoted cholesterol efflux from diseased macrophages and inhibited the development of atherosclerosis.

[0156] Table 9: Lesion area (%) and Oil Red O (lesion area %) in all groups

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[0158] In summary, the results of this study demonstrate the ability of Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, and Bacteroides vulgaris mpk to improve coronary artery disease and related conditions, to lower blood glucose or blood lipid levels, or to improve coronary atherosclerotic lesions.

[0159] Although illustrative embodiments have been shown and described in detail, those skilled in the art will understand that the above embodiments are illustrative and are not intended to limit this disclosure in any way, and that changes, substitutions and modifications may be made to the embodiments without departing from the spirit, principles and scope of this disclosure.

Claims

1. Use of Bacteroides vulgatus in the preparation of a pharmaceutical composition for lowering blood lipid levels in a subject; wherein the Bacteroides vulgatus is Bacteroides vulgatus ATCC 8482.

2. The use according to claim 1, wherein, The pharmaceutical composition comprises a therapeutic or preventative amount of the common Bacteroides.

3. The use according to claim 1, wherein, The pharmaceutical composition is in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, or granules.

4. The use according to claim 1, wherein the pharmaceutical composition further comprises additional agents for treating and / or preventing coronary artery disease, or for lowering blood glucose or blood lipid levels or improving coronary atherosclerotic lesions.

5. The use according to claim 4, wherein the additional agent is selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium channel blockers, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

6. The use according to claim 1, wherein the pharmaceutical composition comprises a concentration of at least 1 x 10⁻⁶. 6 The common Bacteroides cfu / g, or the pharmaceutical composition wherein the drug composition is in liquid form and contains at least 1 x 10⁻⁶ cfu / g. 6 The common Bacteroides cfu / ml.

7. The use according to claim 1, wherein the pharmaceutical composition is administered in conjunction with an additional therapy selected from coronary intervention and coronary artery bypass grafting.

8. The use according to claim 7, wherein, The coronary intervention procedure is angioplasty.

9. The use according to claim 1, wherein the subject is a human.

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