CN107073046A - Purposes of the Bacteroides in prevention and treatment coronary artery disease - Google Patents

Abstract

Bacteroides uniformis is used to treat and/or prevent coronary artery disease preparing, or for reducing the purposes in blood glucose or blood lipid level or preparation for improving coronary atherosclerosis.And the bacteroides uniformis is selected from bacteroides uniformis ATCC 8492, bacteroides uniformis CECT 7771, bacteroides uniformis 0061.

Description

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

Cross References to Related Applications

none

field

The present invention relates to microbiology. Specifically, the present invention relates to the use of bacterial strains of the genus Bacteroides in the preparation of preparations for treating and/or preventing coronary artery disease in subjects or for reducing blood sugar or blood lipid levels or for improving coronary atherosclerotic lesions use. The invention also relates to formulations (such as pharmaceutical, nutraceutical or food compositions) comprising bacteria of the genus Bacteroides. The present invention also relates to a method for treating and/or preventing coronary artery disease or reducing blood sugar or blood lipid levels or improving coronary atherosclerotic lesions in a subject, the method comprising administering an effective amount of Steps for bacterial strains of Bacteroides genus.

background

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 cardiac (ie, heart) muscle, or any part thereof. Typically, CAD is caused by the buildup of plaque on the walls of arteries (ie, atherosclerosis), especially in the large and medium-sized arteries that serve the heart. These conditions have similar causes, mechanisms, and treatments. CAD represents a leading cause of death and morbidity worldwide.

Current knowledge suggests 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 by GWAS (genome-wide association analysis) in recent years, and it has been revealed that 10.6% of genetic factors are represented by 46 common variants (Ehret, G.B. 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 about the influence of environmental factors such as the gut microbiome and the contribution of genes and microbes to disease.

Our "forgotten organ", the gut microbiota, plays a vital role in our health in many ways, such as obtaining energy from food, producing important metabolites, promoting the development and maturation of the immune system, and Protect the host from pathogenic infection, etc. Recent studies have shown that microbiota dysbiosis, chronic inflammation, and metabolic abnormalities are present in the gut in 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, cholesterol) to TMA, which is further oxidized in the liver to TMAO, causing oxidation in blood vessels reaction, which in turn leads to inflammation and lipid deposition, ultimately leading to atherosclerosis and coronary heart disease. At the same time, compared with healthy subjects, the gut microbiota of patients with symptomatic atherosclerosis showed significant abnormalities (Koeth, R.A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient inred meat, promotes atherosclerosis. Nature medicine 19, 576-585, incorporated herein by reference). These studies suggest that gut microbial dysbiosis can significantly affect the pathogenesis of coronary artery disease by inducing metabolic abnormalities in humans. However, the role of gut microbiota dysbiosis in the pathogenesis of atherosclerosis-induced coronary artery disease and its impact on metabolic systems remains puzzling.

summary

The present disclosure aims to solve at least one problem existing in the prior art, at least to some extent.

The present invention is based at least in part on the following findings of the present inventors.

Assessment and characterization of the gut microbiota has become a major area of research in human diseases, including coronary artery disease (CAD). In order to analyze the gut microbial content in CAD patients, the present inventors performed a metagenomic association analysis (MGWAS) protocol 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 2diabetes. Nature 490, 55-60 (2012), incorporated herein by reference).

The present inventors identified 2 species of Bacteroides probiotics. Then, the present inventors respectively verified the effects of the above two Bacteroides probiotics on CAD in animal experiments. The results of animal experiments have proved the ability of Bacteroides uniformis and Bacteroides vulgatus to effectively prevent and treat CAD.

Therefore, in one aspect, the present invention provides Bacteroides monomorpha and/or Bacteroides vulgaris for treating and/or preventing coronary artery disease in a subject, or for reducing blood sugar or blood lipid levels in a subject, Or use in preparations for improving coronary atherosclerotic lesions in subjects.

In a second 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 atherosclerosis in a subject A preparation for sclerosing lesions comprising an effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris.

In a third 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 atherosclerosis in a subject A method for pathological changes, comprising the step of administering an effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris to a subject in need thereof.

In a fourth aspect, the present invention provides Bacteroides monomorpha and/or Bacteroides vulgaris for use in treating and/or preventing coronary artery disease in a subject, or reducing blood sugar or blood lipid levels in a subject, or improving Subjects with coronary atherosclerotic lesions in the method.

Brief description of the drawings

These and other aspects and advantages of the invention will become apparent and more readily understood from the following description taken in conjunction with the accompanying drawings, in which:

Figure 1: The 65 most discriminative MLG species in a random forest model based on 126 MLG markers. Bar lengths indicate the importance of the variable (MLG species).

Figure 2: Bacteroides strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Effect of administration of Bacteroides mpk) on the OGTT curve. Figure 2A: results obtained before (at week 16) administration of Bacteroides strains; Figure 2B: results obtained after administration of Bacteroides strains (at week 24). At week 16, no significant differences were observed in blood glucose levels among all HF-fed groups (Fig. 2A). However, after 8 weeks of gavage treatment (at week 24), the AUC (area under the curve) of blood glucose (mmol/l) was significantly reduced in the B. monomorpha and B. vulgaris groups compared to the AS group (Fig. 2B).

Figure 3: After administration of Bacteroides strains (Bacteroides monomorpha ATCC 8492, B. Quantitative results of atherosclerotic lesion area (n=8/group). Values are shown as mean ± SEM. Differences in values between groups marked with the same letter were not statistically significant according to analysis of variance followed by Tukey's post hoc test (p>0.05). As shown in Figure 3, analysis of atherosclerotic lesions revealed no significant differences between mice administered with different Bacteroides strains for 8 weeks. In contrast, the mean coronary atherosclerotic lesion area was significantly reduced in the 6 groups administered the Bacteroides strain compared with the AS group.

Figure 4: Histological characteristics of atherosclerotic lesions in the aortic root (stained with Oil Red O). A: NC group, B-D: Bacteroides monomorpha group (respectively Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771 and Bacteroides monomorpha 0061); E-G Bacteroides vulgaris groups (respectively Bacteroides B. vulgaris PC510 and B. vulgaris mpk); H: AS group. The results showed that compared with healthy control group (Fig. 4A, NC group), at week 24, mice in the AS group fed a cholesterol-enriched HF diet and a placebo developed a form of aortic root rich in Lipid atherosclerotic lesions (Fig. 4H, AS group); however, foam cells and lipid deposition in the subintimal region of mice administered Bacteroides strains for 8 weeks showed significantly greater decrease (Fig. 4B-4G).

Figure 5: Characterization of atherosclerotic lesion composition by Oil Red O staining of neutral lipids. Values are shown as mean ± SEM. Differences between values of groups marked with the same letter were not statistically significant according to analysis of variance followed by Tukey's post hoc test (p>0.05). The results showed that lipid accumulation was significantly reduced in Bacteroides-treated mice compared with the AS group, suggesting that Bacteroides treatment promoted cholesterol efflux in diseased macrophages and inhibited the development of atherosclerosis .

detail

Terms used herein have meanings as commonly understood by those of ordinary skill in the art to which the present invention pertains. However, for a better understanding of the present invention, definitions and explanations of related terms are provided as follows.

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

According to the present invention, the term "prevent, preventing or prevention" refers to preventing, inhibiting or delaying the occurrence of a disease such as CAD.

According to the present invention, the term "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 development of a disease such as CAD.

According to the present invention, the term "effective amount" refers to an amount effective to achieve the intended purpose. For example, a prophylactically effective amount may be an amount effective or sufficient to prevent, inhibit or delay the occurrence of a disease (such as CAD); a therapeutically effective amount may be an amount effective or sufficient to treat or cure a disease (such as CAD), delaying the symptoms of a disease (such as CAD) The amount of onset and/or delayed progression of a disease such as CAD. Such an effective amount can be readily determined by a person skilled in the art or a physician, and can be determined in accordance with the intended purpose (prevention or treatment), the subject's general health, age, sex, body weight, severity of the disease to be treated, complications , daily use, etc. Determination of such an effective amount is well within the ability of those skilled in the art.

Terms such as "a", "an" and "the" are not only intended to refer to a singular entity, but also include a species that may be illustrated using a specific example. Unless stated in the claims, the terminology herein is used to describe particular embodiments of the invention and is not intended to be limiting of the invention.

In one aspect, the present invention provides Bacteroides uniformis and/or Bacteroides vulgatus in preparation for treating and/or preventing coronary artery disease in a subject, or for reducing Blood glucose or blood lipid levels or use in preparations for improving coronary atherosclerotic lesions in subjects.

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

In a preferred embodiment, the formulation may comprise any strain of Bacteroides vulgaris or any combination thereof. For example, the formulation may comprise one or more strains of Bacteroides vulgaris, eg at least 2, 3, 4, 5 or more strains. In a preferred embodiment, the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof.

In a preferred embodiment, Bacteroides monomorpha and Bacteroides vulgaris as described above may be used in combination. Thus, the formulation may comprise one or more strains of Bacteroides monomorpha and one or more strains of Bacteroides vulgaris.

In a preferred embodiment, the formulation is a pharmaceutical composition. Such pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical art. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders or granules.

In a preferred embodiment, said formulation is a nutraceutical or food composition. Such compositions may be in solid, semi-solid or liquid form. In a preferred embodiment, the preparation is a dairy product, such as milk, milk powder or yoghurt.

In a preferred embodiment, the formulation further comprises additional agents for the treatment and/or prevention of coronary artery disease, or for lowering blood glucose or blood lipid levels or for ameliorating coronary atherosclerotic lesions. Such additional agents may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

Additionally, where the formulation comprises Bacteroides monomorpha, the additional agent may comprise any strain of Bacteroides vulgaris such as B. vulgaris ATCC 8482, B. vulgaris PC510, B. vulgaris mpk, or any combination thereof. Similarly, where the formulation comprises Bacteroides vulgaris, the additional agent may include any strain of Bacteroides monomorpha, for example Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061 or any combination thereof.

In a preferred embodiment, the formulation comprises a unit dose of Bacteroides monomorpha and/or Bacteroides vulgaris, for example, at a concentration of at least 1x10 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 Bacteroides monomorpha and/or Bacteroides vulgaris. Where the formulation is in the form of a liquid (eg, solution, suspension, emulsion), it may comprise a concentration of at least 1x10 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 monomorpha and/or Bacteroides vulgaris.

In preferred embodiments, the formulations may be administered with additional therapies. This additional therapy can be any therapy known for coronary artery disease, such as coronary intervention (eg, angioplasty), and coronary artery bypass grafting.

In preferred embodiments, the subject is a mammal, such as a human.

In a second 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 atherosclerosis in a subject A preparation for a lesion comprising an effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris.

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

In a preferred embodiment, the formulation may comprise any strain of Bacteroides vulgaris or any combination thereof. For example, the formulation may comprise one or more strains of Bacteroides vulgaris, eg at least 2, 3, 4, 5 or more strains. In a preferred embodiment, the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof.

In a preferred embodiment, Bacteroides monomorpha and Bacteroides vulgaris as described above may be used in combination. Thus, the formulation may comprise one or more strains of Bacteroides monomorpha and one or more strains of Bacteroides vulgaris.

In a preferred embodiment, the formulation is a pharmaceutical composition. Such pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical art. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders or granules.

In a preferred embodiment, said formulation is a nutraceutical or food composition. Such compositions may be in solid, semi-solid or liquid form. In a preferred embodiment, the preparation is a dairy product, such as milk, milk powder or yoghurt.

In a preferred embodiment, the formulation further comprises additional agents for the treatment and/or prevention of coronary artery disease, or for lowering blood glucose or blood lipid levels or for ameliorating coronary atherosclerotic lesions. Such additional agents may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin, and any combination thereof.

Additionally, where the formulation comprises Bacteroides monomorpha, the additional agent may comprise any strain of Bacteroides vulgaris such as B. vulgaris ATCC 8482, B. vulgaris PC510, B. vulgaris mpk, or any combination thereof. Similarly, where the formulation comprises Bacteroides vulgaris, the additional agent may include any strain of Bacteroides monomorpha, for example Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061 or any combination thereof.

In a preferred embodiment, the formulation comprises a unit dose of Bacteroides monomorpha and/or Bacteroides vulgaris, for example, at a concentration of at least 1x10 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 Bacteroides monomorpha and/or Bacteroides vulgaris. Where the formulation is in the form of a liquid (eg, solution, suspension, emulsion), it may comprise a concentration of at least 1x10 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 monomorpha and/or Bacteroides vulgaris.

In preferred embodiments, the formulations may be administered with additional therapies. This additional therapy can be any therapy known for coronary artery disease, such as coronary intervention (eg, angioplasty), and coronary artery bypass grafting.

In preferred embodiments, the subject is a mammal, such as a human.

In a third 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 atherosclerosis in a subject A method for pathological changes, comprising the step of administering an effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris to a subject in need thereof.

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

In preferred embodiments, any strain of Bacteroides vulgaris or any combination thereof may be administered to the subject. For example, one or more strains of Bacteroides vulgaris, eg, at least 2, 3, 4, 5 or more strains, may be administered to the subject. In a preferred embodiment, the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof.

In a preferred embodiment, Bacteroides monomorpha and Bacteroides vulgaris as described above may be used in combination. Thus, one or more strains of Bacteroides monomorpha and one or more strains of Bacteroides vulgaris may be administered to the subject.

In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be formulated and administered as a pharmaceutical composition. Such pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical art. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders or granules.

In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be formulated and administered as a nutraceutical or food composition. Such compositions may be in solid, semi-solid or liquid form. In a preferred embodiment, such a composition is a dairy product, such as milk, milk powder or yoghurt.

In a preferred embodiment, the method further comprises administering an additional agent for treating and/or preventing coronary artery disease, or reducing blood glucose or blood lipid levels, or ameliorating coronary atherosclerotic lesions. This additional agent may be administered before, simultaneously with or after administration of Bacteroides monomorpha and/or Bacteroides vulgaris.

In preferred embodiments, such additional agents may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin and random combination.

Additionally, where Bacteroides monomorpha is administered to a subject, the additional agent may include any strain of Bacteroides vulgaris, such as Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, or any combination thereof . Similarly, where Bacteroides vulgaris is administered 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.

In a preferred embodiment, 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 1×10 ¹¹ cfu/kg, or at least 1×10 ¹² cfu/kg body weight of the subject, Bacteroides monomorpha and/or Bacteroides vulgaris are administered. In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be administered 3 times a day, 2 times a day, once a day, once every two days or once a week.

In preferred embodiments, the method further comprises administering an additional therapy. This additional therapy can be any therapy known for coronary artery disease, such as coronary intervention (eg, angioplasty), and coronary artery bypass grafting.

In preferred embodiments, the subject is a mammal, such as a human.

In a fourth aspect, the present invention provides Bacteroides monomorpha and/or Bacteroides vulgaris for use in treating and/or preventing coronary artery disease in a subject, or reducing blood sugar or blood lipid levels in a subject, or improving Subjects with coronary atherosclerotic lesions in the method.

In a preferred embodiment, any strain of Bacteroides monomorpha or any combination thereof may be used in the method. For example, one or more strains of Bacteroides monomorpha, such as at least 2, 3, 4, 5 or more strains, can be used in the method. In a preferred embodiment, the Bacteroides monomorpha is selected from the group consisting of Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061 and any combination thereof.

In a preferred embodiment, any strain of Bacteroides vulgaris or any combination thereof may be used in the method. For example, one or more strains of Bacteroides vulgaris, such as at least 2, 3, 4, 5 or more strains, can be used in the method. In a preferred embodiment, the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof.

In a preferred embodiment, Bacteroides monomorpha and Bacteroides vulgaris as described above may be used in combination. Thus, one or more strains of Bacteroides monomorpha and one or more strains of Bacteroides vulgaris can be used in this method.

In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be formulated and administered as a pharmaceutical composition. Such pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of Bacteroides monomorpha and/or Bacteroides vulgaris. In a preferred embodiment, the pharmaceutical composition may be in any form known in the medical art. For example, the pharmaceutical composition may be in the form of tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders or granules.

In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be formulated and administered as a nutraceutical or food composition. Such compositions may be in solid, semi-solid or liquid form. In a preferred embodiment, such a composition is a dairy product, such as milk, milk powder or yoghurt.

In a preferred embodiment, Bacteroides monomorpha 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 blood lipid levels or for ameliorating coronary atherosclerotic lesions . This additional agent may be administered before, simultaneously with or after administration of Bacteroides monomorpha and/or Bacteroides vulgaris.

In preferred embodiments, such additional agents may be selected from cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, calcium channel blockers, aspirin and random combination.

Additionally, where Bacteroides monomorpha is administered to a subject, the additional agent may include any strain of Bacteroides vulgaris, such as Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, or any combination thereof . Similarly, where Bacteroides vulgaris is administered 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.

In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be present 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 The amount is administered in cfu/kg, at least 1x1010 cfu/kg, at least ^1x1011 cfu/kg, or at least ^{1x1012 cfu} /kg body weight of the subject. In a preferred embodiment, Bacteroides monomorpha and/or Bacteroides vulgaris may be administered 3 times a day, 2 times a day, once a day, once every two days or once a week.

In preferred embodiments, Bacteroides monomorpha and/or Bacteroides vulgaris may be administered with additional therapy. This additional therapy can be any therapy known for coronary artery disease, such as coronary intervention (eg, angioplasty), and coronary artery bypass grafting.

In preferred embodiments, the subject is a mammal, such as a human.

The invention is further illustrated in the following non-limiting examples. Parts and percentages are by weight and degrees Celsius unless otherwise indicated. The reagents used are all 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

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

1.1: Sample collection

In 2011, Guangdong Provincial People's Hospital collected fecal samples from 165 subjects in southern China, including 88 patients with atherosclerotic cardiovascular disease (ACVD) and 77 control subjects (training group ,Table 1). Patients with ACVD were diagnosed and classified according to pathological features. 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.

This study has obtained full ethical approval and all patients gave written informed consent. The study was approved by the Institutional Review Board of Guangdong General Hospital.

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

Note: Information on gender was unknown for one of 88 patients and for two of 77 control subjects.

1.2: DNA extraction

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

1.3: DNA library construction and sequencing

DNA libraries were constructed following the manufacturer's instructions (Illumina). The inventors used conventional workflows for DNA clustering, template hybridization, isothermal amplification, single-strandization, blocking and denaturation, and hybridization of sequencing primers. The present inventors constructed a paired-end (PE) sequencing library with an insert size of 350 bp in each sample, followed by high-throughput sequencing to obtain about 30 million PE reads with a length of 2×100 bp (reads). High-quality reads were obtained by filtering from Illumina raw reads to remove low-quality reads with ambiguous 'N' bases, adapter contamination, and human DNA contamination and simultaneously by trimming low-quality terminal bases in the reads.

The present inventors output a total of about 4.77Gb 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).

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

1.4: Processing and analysis of metagenomic data

1.4.1: Gene catalog construction

Gene catalog construction. By using the same parameters (Qin, J. et al. Ametagenome-wide association study of gut microbiota in type 2 diabetes.Nature490,55-60 (2012), incorporated herein by reference) as used to construct the type 2 diabetes gene catalog, this 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) to 165 High-quality reads from samples were de novo assembled and gene predicted. All predicted genes were pairwise aligned using BLAT, and genes whose sequences over 90% of their length were aligned to another gene with greater than 95% identity were removed as redundancy ( Gaps are not allowed), resulting in a non-redundant gene catalog (4.5M gene catalog) containing 4,537,046 genes.

Taxonomic assignment of genes. Taxonomic assignment of predicted genes was performed using an in-house pipeline described in a published T2D paper (Qin et al., 2012, supra).

1.4.2: Construction of data set (data profile)

Gene profile. The above 4,537,046 genes and their relative abundance in 165 samples were used to construct a gene profile for association studies (the inventors used the same gene as described in the published T2D paper (Qin et al. 2012, supra). method to calculate relative gene abundance.

IMG species and mOTU species profiles. Total fecal valid reads were compared with 4,653 reference genomes from IMG v400 using default parameters (Markowitz, V.M. et al., IMG: the integrated microbial genomes database and comparative analysis system. Nucleic acids research 40, D115-D122 (2012), by reference and included in this paper) and 79,268 sequences referenced by mOTU (Sunagawa, S. et al. Metagenomicspecies profiling using universal phylogenetic marker genes. Nature methods10, 1196-1199 (2013), incorporated herein by reference) for comparison. 1290 IMG species (species shared among at least 10 subjects) and 560 mOTU species were identified.

1.4.3: Analysis of factors affecting the genetic profile of the gut microbiota. The inventors used permutational multivariate analysis of variance (PERMANOVA) to assess 25 different characteristics (including CAD status, HDLC, CHOL, gender, 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 gene profiles of the 4.5M reference gene catalog. The present inventors performed the analysis using the method implemented in the software package "vegan" in the R software, and obtained p-values for the permutations by 10,000 permutations. The inventors also used "p.adjust" in R software and the Benjamini-Hochberg method to adjust for multiple testing to obtain the q-value for each test. PERMANOA identified two significant factors (based on gene profiles) associated with gut microbiota (q<0.05, Table 3). Analysis revealed that CAD and HDLC status were the most significantly associated markers, suggesting that disease status is a major determinant of gut microbiota composition. Gender, age and some CAD clinical indicators such as CHOL, FGB, hypertension and APOB are also important factors.

Table 3: PERMANOVA based on Euclidean distance analysis of gene profiles. This analysis was used to test whether clinical parameters and ACVD status had a significant effect on the gut microbiota (ie, q-value <0.05).

1.4.4: Identification of ACVD-related markers

Identification of ACVD-associated genes. To identify the association between the metagenomic profile and ACVD, a two-tailed Wilcoxon rank sum test was performed on the 2.1M high-occurrence genes (genes present in less than 10 samples out of all 165 samples were removed) profiles. A total of 438,750 gene markers (20.48% of 2.1M genes) were obtained that were enriched in patients or control subjects with p-value<0.01 and FDR=2.23%.

Estimate the false discovery rate (FDR). Instead of the sequential p-value rejection method (sequential p-value rejection method) to estimate FDR.

Receiver operating characteristic (ROC) analysis. The inventors applied ROC analysis to evaluate the performance of metagenomic marker-based ACVD classification. Then, the inventors used the "pROC" package in R software to plot the ROC curve.

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

126 MLG species based on gene profiles of 438,750 ACVD-associated markers. The present inventors constructed a metagenomic linkage group (MLG) using 438,750 gene markers by the same method as described in the published T2D paper (Qin et al., 2012, supra). All 438,750 genes were annotated by aligning these genes to the 4,653 reference genomes in IMG v400. If more than 50% of the constitutive genes in an MLG were annotated to a genome, the MLG was assigned to the genome, otherwise it was called unclassified. A total of 136 MLG genomes with more than 550 genes were selected. MLG genomes belonging to the same species were grouped together to construct MLG species. Finally, the inventors obtained 127 MLG species. The present inventors performed the Wilcoxon rank sum test on 127 MLG species using the Benjamini-Hochberg adjustment method, among 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 average abundance of the genes of the MLG species after removing 5% of the lowest and 5% of the highest abundance genes (Qin et al., 2012, supra).

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

Identification of MLG species markers. To identify MLG species markers, the inventors analyzed 126 ACVD-associated 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 the 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 people. Finally, the MLG marker set (including 65 MLG species) with the lowest false prediction rate was selected as the MLG species marker (Fig. 1), where the false negative (FN) rate was 6.8% and the false positive (FP) rate was 3.89% . In addition, the inventors used the OOB (out-of-bag data) disease prediction probability from the randomForest model based on the selected MLG species markers to draw the ROC curve, and calculated the area under the ROC curve to be 98.17% using the R package "pROC".

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

1.4.6: Identification of ACVD-associated IMG species and mOTU species. IMG species and mOTU species markers were identified based on IMG species and mOTU species profiles. The inventors identified ACVD-associated IMG species and mOTU species (q<0.05) (Wilcoxon rank sum test with Benjamini-Hochberg adjustment). Subsequently, IMG species markers and mOTU species markers were selected using the randomForest method (as in the selection of MLG species markers).

The 65 IMG species with ROC of 98.52% and the 15 mOTU species with ROC of 96.16% also clearly distinguished CAD patients from healthy subjects according to Wilcoxon rank sum test and random forest selection (q<0.05; see Table 5 and 6). Similar to the 65 MLG species markers, among the 65 IMG species markers and 15 mOTU species markers, the inventors found that Bacteroides monomorpha was significantly enriched in the control group.

Example 2: Validation in Animal Experiments Related to CAD

In order to verify the ability of probiotics Bacteroides monomorpha and Bacteroides vulgaris in preventing and treating CAD-related diseases, the inventors conducted animal experiments.

2.1: Methods

In order to study the inhibitory effect of Bacteroides monomorpha and Bacteroides vulgaris on the aortic plaque area of mouse atherosclerosis, mice were fed a high-fat diet for 16 weeks to establish an atherosclerosis model, and then administered from the 16th week Bacteroides monomorpha and Bacteroides vulgaris, and the effects on blood sugar and OGTT (Oral Glucose Tolerance Test), blood lipids and atherosclerotic plaque area were observed.

2.1.1: Animals and treatments

Sixty-four male Specific Pathogen Free (SPF) C57BL/6J mice (10 weeks old), weighing 22.5-25.9 g, were purchased from the Experimental Animal Center of Southern Medical University, China. Mice used in diet-induced atherosclerosis studies had access to drinking water and food diets ad libitum for 2 weeks of acclimatization. They were then randomly divided into 2 parts: one part (8 mice) was fed a normal chow diet (NC group, 10% of calories from fat and 3.85 total kcal per gram of diet, purchased from Research Diets, Inc. , New Brunswick, NJ, USA) as a healthy control. Another part (56 mice) was fed a high-fat diet with 2% cholesterol for the induction of atherosclerosis (60% of the calories in this diet came from fat and contained 5.24 total kcal per gram of diet, which was purchased from Research Diets , Inc.), after 16 weeks, the 56 mice were randomly divided into 7 groups (8 mice in each group). One group, serving as the atherosclerotic control group (AS group), was given the same cholesterol-enriched HF diet as above, and received 200 μl of Columbia blood medium (DSMZ Medium 693) as a placebo. The other 6 groups (groups B1-B6) also received cholesterol-rich HF diet, and administered 200 μl of 6 candidate probiotic strains (namely Bacteroides monomorphum ATCC 8492, Bacteroides monomorpha Bacteroides CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510 and Bacteroides vulgaris mpk), the above strains are suspended in Columbia blood medium at a concentration of 10 ⁹ - 10 ¹⁰ cfu/ml (prepared fresh weekly). The above-mentioned mice were further fed for 8 weeks.

Bacteroides monomorpha ATCC 8492 and Bacteroides vulgaris ATCC 8482 were purchased from the American Type Culture Collection (ATCC).

Bacteroides monomorpha CECT 7771 was purchased from the Spanish Collection of General Microorganisms.

Bacteroides monomorpha 0061 was obtained from Virginia Tech Anaerobe Laboratory Culture Collection (Shoemaker, N.B., & Salyers, A.A. (1988). Tetracycline-dependent appearance of plasmamid like forms in Bacteroides uniformis 0061 mediated by conjugalBacteroides tetracycline resistance elements. Journal of bacteriology, 170(4), 1651-1657).

Bacteroides vulgatus PC510 was obtained from the CSIRO Preventive Health Flagship Research Program and the Animal Husbandry Industry Department (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 ).

Bacteroides vulgatus mpk was obtained from the Institute of Medical Microbiology and Hygiene, University of Tübingen (Waidmann M et al. 77).

The strains were purified and grown using anaerobic culture techniques. The composition of the Columbia blood medium used for the 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 strains were grown anaerobically at 37°C for 48 hours.

2.1.2: Oral Glucose Tolerance Test (OGTT)

After fasting for 8 hours, glucose was orally administered to the mice at a dose of 2.0 g/kg body weight. Blood samples were taken from the tail before and 15, 30, 60 and 120 minutes after glucose administration, and blood glucose levels were measured with a glucometer (Roche Diagnostics, Mannheim, Germany). Blood glucose levels before glucose administration represent fasting blood glucose levels.

2.1.3: Collection of blood and aorta

At the end of week 24, after a 12-hour fast, all blood was collected from the orbital plexus and 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 sacrificed by cervical dislocation. Plasma triglyceride (TG) and plasma total cholesterol (TC) were measured using a kit (Nanjing Jiancheng Bio-engineering Institute, China) that combined enzymatic reaction and spectrophotometric detection of the final plasma product of the reaction. Aortas were collected and processed for cross-sectional analysis of plaque area in the aortic root.

2.1.4: Assessment of atherosclerotic plaque

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

2.2: Results

2.2.1: Effects on blood glucose and OGTT

At week 16, no significant differences were observed in blood glucose levels among all HF-fed groups (Fig. 2A). However, after 8 weeks of gavage treatment (week 24), an AUC of blood glucose (mmol/l) in the B. monomorpha and B. vulgaris groups was observed in the oral glucose tolerance test compared to the AS group (Area under the curve) decreased significantly ( FIG. 2B ), and the AUC data of each group are shown in Table 7.

Table 7: AUC values of OGTT curves for each group. Each value is shown as mean ± SEM. Differences between values for groups marked with the same letter were not statistically significant according to analysis of variance followed by Tukey's post hoc test. Between individual groups, the same letter marked indicates that the value of the marked group was not significantly different (p > 0.05) as determined by Tukey's test.

2.2.2: Effects on serum lipids

The results on serum lipids for the administration of Bacteroides monomorpha ATCC 8492, CECT 7771 and 0061 and Bacteroides vulgaris ATCC 8482, PC510 and mpk are shown in Table 8. Treatment with a cholesterol-enriched HF diet combined with placebo gavage significantly increased plasma triglycerides and plasma total cholesterol compared with the NC group. However, serum lipid levels were significantly lower in the B. monomorpha and B. vulgaris gavage groups compared with the AS group.

Table 8: Effect of administration of Bacteroides strains on plasma triglycerides (TG) and plasma total cholesterol (TC). Each value is shown as mean ± SEM. Differences between values for groups marked with the same letter were not statistically significant according to analysis of variance followed by Tukey's post hoc test. Between individual groups, the same letter marked indicates that the value of the marked group was not significantly different (p > 0.05) as determined by Tukey's test.

2.2.3: The effect of using Bacteroides strains to treat coronary atherosclerotic lesions in mice

Figure 3 shows the mice after administration of Bacteroides strains (Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510 or Bacteroides vulgaris mpk) Quantitative results of coronary atherosclerotic lesion area (n=8/group). Values are shown as mean ± SEM. Differences between groups marked with the same letter were not statistically significant according to analysis of variance followed by Tukey's post hoc test (p>0.05).

As shown in Figure 3, analysis of atherosclerotic lesions revealed no significant differences between mice administered with different Bacteroides strains for 8 weeks. In contrast, the mean coronary atherosclerotic lesion area was significantly reduced in the 6 groups administered the Bacteroides strain compared to the AS group ( FIG. 3 , Table 9 ).

As shown by the histological features of the longitudinal sections of the aortic root, mice in the AS group fed a cholesterol-enriched HF diet and placebo, compared with the healthy control group (Fig. 4A, NC group), at 24 weeks Lipid-rich atherosclerotic lesions formed in the aortic root (Fig. 4H, panel AS). In contrast, foam cells and lipid deposition were significantly reduced in the subintimal region of mice administered the Bacteroides strain for 8 weeks compared to the AS group ( FIGS. 4B-4G ).

Differences in lipid accumulation indicated that Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, and Bacteroides vulgaris mpk induced a cholesterol-rich HF diet, respectively. Atherosclerosis development in a mouse model of atherosclerosis has a mitigating effect. Quantitative detection of lipid accumulation in atherosclerotic lesions by Oil Red O staining showed a significant reduction in lipid accumulation in Bacteroides-treated mice compared to the AS group (Fig. 5, Table 9). These results suggest that Bacteroides treatment promotes cholesterol efflux from diseased macrophages and inhibits the development of atherosclerosis.

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

In summary, the results of this study demonstrate the usefulness of Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, and Bacteroides vulgaris mpk in improving coronary artery disease and Related diseases, for reducing blood sugar or blood lipid levels, or for improving the ability of coronary atherosclerotic lesions.

While illustrative embodiments have been shown and described in detail, it should be understood by those skilled in the art that the foregoing embodiments are illustrative and not intended to limit the present disclosure in any way, and may be modified without departing from the spirit of the present disclosure. Changes, substitutions and modifications are made to the described embodiments within the context of , principles and scope.

Claims (40)

1. Bacteroides uniformis is used in the preparation for treating and/or preventing coronary artery disease in subjects, or for reducing blood sugar or blood lipid levels in subjects, or for improving coronary atherosclerosis in subjects Use in the preparation of sclerotic lesions. 2. The use according to claim 1, wherein the Bacteroides monomorpha is selected from Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061 and any combination thereof. 3. The use according to claim 1 or 2, wherein the preparation is a pharmaceutical composition, preferably comprising a therapeutically or prophylactically effective amount of Bacteroides monomorpha, and optionally a tablet, pill, suspension, emulsion , solution, gel, capsule, powder or granule form. 4. Use according to claim 1 or 2, wherein the formulation is a nutraceutical or food composition, optionally in solid, semi-solid or liquid form, and preferably a dairy product, such as milk, powdered milk or yoghurt. 5. according to the purposes described in any one in claim 1-4, wherein said preparation also comprises for treating and/or preventing coronary artery disease, or reducing blood sugar or blood fat level or improving coronary atherosclerotic pathological change additionally medicine. 6. Use according to claim 5, wherein the additional agent is selected from the group consisting of Bacteroides vulgaris, cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, Calcium channel blockers, aspirin, and any combination thereof. 7. The use according to claim 6, wherein the Bacteroides vulgaris is selected from Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk and any combination thereof. 8. Use according to any one of claims 1-7, wherein the formulation comprises a concentration of at least ^1x106 cfu/g, such as at least ^1x107 cfu/g, at least ^1x108 cfu/g, at least ^1x109 cfu /g, at least 1x10 ¹⁰ cfu/g, at least 1x10 ¹¹ cfu/g, or at least 1x10 ¹² cfu/g Bacteroides monomorpha, or wherein the preparation is in liquid form and contains a concentration of at least 1x10 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 monomorpha. 9. The use according to any one of claims 1-8, wherein the formulation is administered with additional therapy, such as coronary intervention (eg angioplasty) and coronary artery bypass grafting. 10. The use according to any one of claims 1-9, wherein the subject is a mammal such as a human. 11. A preparation for treating and/or preventing coronary artery disease in a subject, or for reducing blood sugar or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, The formulation comprises an effective amount of Bacteroides monomorpha. 12. The formulation of claim 11, wherein the Bacteroides monomorpha is selected from the group consisting of Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, and any combination thereof. 13. The formulation according to claim 11 or 12, wherein the formulation is a pharmaceutical composition, preferably comprising a therapeutically or prophylactically effective amount of Bacteroides monomorpha, and optionally a tablet, pill, suspension, emulsion , solution, gel, capsule, powder or granule form. 14. The formulation according to claim 11 or 12, wherein the formulation is a nutraceutical or food composition, and is optionally in solid, semi-solid or liquid form, and is preferably a dairy product, such as milk , Milk Powder Or Yogurt. 15. The preparation according to any one of claims 11-14, wherein the preparation further comprises another medicine for treating and/or preventing coronary artery disease, or reducing blood sugar or blood lipid levels or improving coronary atherosclerotic lesions medicine. 16. The formulation according to claim 15, wherein the additional agent is selected from the group consisting of Bacteroides vulgaris, cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, Calcium channel blockers, aspirin, and any combination thereof. 17. The formulation of claim 16, wherein the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris and any combination thereof. 18. The formulation according to any one of claims 11-17, wherein the formulation comprises a concentration of at least ^1x106 cfu/g, such as at least ^1x107 cfu/g, at least ^1x108 cfu/g, at least ^1x109 cfu monomorphic bacteria/g, at least 1x10 ¹⁰ cfu/g, at least 1x10 ¹¹ cfu/g, or at least 1x10 ¹² cfu/g, or wherein the preparation is in liquid form and comprises a concentration of at least 1x10 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 monomorpha. 19. The formulation according to any one of claims 11-18, wherein the formulation is administered with additional therapy such as coronary intervention (such as angioplasty) and coronary artery bypass grafting surgery. 20. The formulation according to any one of claims 11-19, wherein the subject is a mammal such as a human. 21. A method for treating and/or preventing coronary artery disease in a subject, or for reducing blood sugar or blood lipid levels in a subject, or for improving coronary atherosclerotic lesions in a subject, It includes the step of administering to a subject in need thereof an effective amount of Bacteroides monomorpha. 22. The method of claim 21, wherein the Bacteroides monomorpha is selected from the group consisting of Bacteroides monomorpha ATCC 8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061, and any combination thereof. 23. The method according to claim 21 or 22, wherein said Bacteroides monomorpha is formulated and administered as a pharmaceutical composition, optionally a tablet, pill, suspension, emulsion, In the form of solutions, gels, capsules, powders or granules. 24. The method according to claim 21 or 22, wherein the Bacteroides monomorpha is formulated and administered as a nutraceutical or food composition, optionally solid, semi-solid or liquid form, and preferably a dairy product such as milk, milk powder or yoghurt. 25. The method according to any one of claims 21-24, wherein the method further comprises administering a drug for treating and/or preventing coronary artery disease, or reducing blood sugar or blood lipid levels, or improving coronary atherosclerotic lesions wherein preferably, the additional agent is administered before, simultaneously or after the administration of the Bacteroides monomorpha. 26. The method of claim 25, wherein the additional agent is selected from the group consisting of Bacteroides vulgaris, cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE inhibitors, Calcium channel blockers, aspirin, and any combination thereof. 27. The method of claim 26, wherein the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC 8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof. 28. The method according to any one of claims 21-27, wherein 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 The Bacteroides monomorpha is administered in an amount of ⁹ cfu/kg, at least 1x1010 cfu/kg, at least ^1x1011 cfu/kg, or at least ^{1x1012 cfu} /kg of the subject's body weight, and preferably 3 times a day, The Bacteroides monomorpha is administered twice a day, once a day, once every two days or once a week. 29. The method according to any one of claims 21-28, wherein the method further comprises administering additional therapy, such as coronary intervention (eg, angioplasty) and coronary artery bypass grafting. 30. The method according to any one of claims 21-29, wherein the subject is a mammal such as a human. 31. A Bacteroides monomorpha used for treating and/or preventing coronary artery disease in a subject, or for reducing blood sugar or blood lipid levels in a subject or improving coronary atherosclerotic lesions in a subject method. 32. The Bacteroides monomorpha according to claim 31, wherein the Bacteroides monomorpha is selected from the group consisting of Bacteroides monomorpha ATCC8492, Bacteroides monomorpha CECT 7771, Bacteroides monomorpha 0061 and any combination thereof. 33. The Bacteroides monomorpha according to claim 31 or 32, wherein the Bacteroides monomorpha is formulated and administered as a pharmaceutical composition, optionally a tablet, pill, suspension, In the form of emulsions, solutions, gels, capsules, powders or granules. 34. Bacteroides monomorpha according to claim 31 or 32, wherein said Bacteroides monomorpha is formulated and administered as a nutraceutical or food composition, said composition being optionally solid, semi-solid or liquid form, and preferably a dairy product such as milk, milk powder or yoghurt. 35. Bacteroides monomorpha according to any one of claims 31-34, wherein said Bacteroides monomorpha is administered in combination with an additional agent for the treatment and/or prevention of coronary artery disease, Or reduce blood sugar or blood lipid levels or improve coronary atherosclerotic lesions, wherein preferably, the additional agent is administered before, simultaneously or after the administration of the Bacteroides monomorpha. 36. Bacteroides monomorpha according to claim 35, wherein said additional agent is selected from the group consisting of Bacteroides vulgaris, cholesterol-lowering drugs, beta-blockers, nitroglycerin, calcium antagonists, statins, nitroglycerin, ACE Inhibitors, calcium channel blockers, aspirin, and any combination thereof. 37. The Bacteroides monomorpha according to claim 36, wherein the Bacteroides vulgaris is selected from the group consisting of Bacteroides vulgaris ATCC8482, Bacteroides vulgaris PC510, Bacteroides vulgaris mpk, and any combination thereof. 38. Bacteroides monomorpha according to any one of claims 31-37, wherein said Bacteroides monomorpha is at least 1×10 ⁵ cfu/kg, such as at least 1×10 ⁶ cfu/kg, at least 1×10 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 cfu/kg of said subject's body weight, and preferably said single Bacteroides were administered 3 times a day, 2 times a day, once a day, once every two days or once a week. 39. Bacteroides monomorpha according to any one of claims 31-38, wherein said Bacteroides monomorpha is administered together with an additional therapy such as coronary intervention (eg angioplasty) and coronary artery bypass grafting. 40. Bacteroides monomorpha according to any one of claims 31-39, wherein the subject is a mammal such as a human.