KR20220029869A - A composition for diagnosing brain cancer in a high salt environment - Google Patents

Abstract

The present invention relates to a composition for diagnosing brain tumors in a high salt environment using intestinal microorganisms, which can diagnose brain tumors in the very early stage through a very easy method by detecting a strain existing level.

Description

A composition for diagnosing brain tumor in a high salt environment {A composition for diagnosing brain cancer in a high salt environment}

The present invention relates to a composition for diagnosing brain tumors in a high-salt environment.

Sodium is a major component of tissues and fluids in our body and is an inorganic nutrient that regulates osmotic pressure inside and outside cells. In addition to salt, it is included in almost all foods, including natural foods such as vegetables, fruits, grains, meat, and fish, as well as seasonings (MSG), baking powder, soy sauce, sausage, ham, bacon, ketchup, chili sauce, and mustard. According to the World Health Organization (WHO), the daily recommended amount of sodium for healthy adults is 2,000 mg (based on a body weight of 50 kg), but the average daily sodium intake for Koreans in 2010 was 4,878 mg (National Health and Nutrition Examination Survey 2010). It is more than 2.4 times higher than the recommended amount of the World Health Organization (WHO), and in particular, for men aged 30 to 50, it is 6,621 mg, which is more than three times higher. Moreover, the average sodium intake of Koreans is increasing every year from 4388 mg in 2007 to 4831 mg in 2011. Studies on a high-salt diet, which consume a large amount of sodium, have mainly focused on cardiovascular diseases. A study was published (Int J Oncol. 2017 May; 50(5): 1477-1481). However, studies on the effect of a high-salt diet on the antitumor immune response are still insufficient.

On the other hand, microbiota, which refers to all microorganisms that coexist in the human body, refers to a microbial community including bacteria, archaea, and eukaryotes that exist in a specific environment, and intestinal microbes Guns play an important role in human physiology, and are known to have a major impact on human health and disease through interaction with human cells. A high-salt diet is also expected to influence the immune response by inducing changes in the intestinal symbiotic microorganisms, but there is no technology yet to elucidate the relationship between a high-salt diet, the intestinal microflora, and the occurrence of cancer.

Accordingly, the present invention has been devised to solve the above problems, and relates to a composition for diagnosing brain tumors in a high-salt environment using intestinal microorganisms.

One object of the present invention is to provide a method for predicting the risk of developing a brain tumor in a high-salt individual.

Another object of the present invention is to provide a method for providing information on brain tumor diagnosis in subjects with high salt diet.

Another object of the present invention is to provide a composition for diagnosing brain tumors in individuals with high salt diet, and a kit for diagnosing brain tumors comprising the same.

Another object of the present invention is to provide a composition for promoting brain tumor development, and a method for preparing a brain tumor animal model using the same.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those of ordinary skill in the art from the following description.

Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, various specific details are set forth, such as specific forms, compositions, processes, and the like, for a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well-known processes and manufacturing techniques have not been described in specific detail in order not to unnecessarily obscure the present invention. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, references to "in one embodiment" or "an embodiment" in various places throughout this specification do not necessarily refer to the same embodiment of the invention. Additionally, the particular features, forms, compositions, or properties may be combined in any suitable way in one or more embodiments.

Unless otherwise defined in the specification, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The "high salt intake" of the present invention refers to a meal in which a large amount of sodium is ingested in excess of 2,000 mg (5 g of salt) daily sodium recommended by the World Health Organization (WHO) based on an adult body weight of 50 kg. According to the results of the 2015 National Nutrition Survey, the average daily sodium intake for Koreans over the age of 19 is 4,111.3 mg. . Also, according to the Food and Drug Safety Evaluation Institute under the Ministry of Food and Drug Safety, the average daily sodium intake for men was 5503 mg, which was higher than that of women, 3,908 mg.

The term "intestinal microflora" of the present invention refers to a microbial community including bacteria, archaea, and eukaryotes existing in the intestine of an individual. The gut microbiota plays an important role in human physiology, and is known to have a major impact on human health and disease through interaction with human cells. In particular, it is known that the number of symbiotic microorganisms in the human body reaches 100 trillion, 10 times more than human cells, and the number of genes in microorganisms is more than 100 times that of human genes. The symbiotic bacteria in our body secrete nanometer-sized vesicles to exchange information such as genes and proteins with other cells. The mucous membrane forms a physical barrier that does not allow particles larger than 200 nanometers (nm) to pass through. However, bacteria that coexist on the mucosa cannot pass through the mucosa, but bacterial vesicles are usually less than 100 nanometers in size. It freely passes through the mucous membrane and is absorbed into our body. Metagenomics, also called environmental genomics, can be said to be the analysis of metagenomic data obtained from samples collected from the environment (Korean Patent Publication No. 2011-0073049). Recently, it has become possible to list the bacterial composition of the human microbiota by a method based on the 16s ribosomal RNA (16s rRNA) sequencing. , NGS) platform to analyze. However, in the onset of brain tumors, there has been no report on a method for identifying the causative factors of brain tumors and predicting brain tumors through intestinal microbiome metagenome analysis.

The "Bacteroides sp. strain" of the present invention is a Gram-negative anaerobic bacterium, and 40-48% of the DNA base is composed of G (guanine) and C (cytosine). The Bacteroides sp. strain is, for example, Bacteroides vulgatus ( Bacteroides vulgatus ), Bacteroides acidifaciens ( Bacteroides acidifaciens ), Bacteroides barnesiaes ( Bacteroides barnesiaes ), Bacteroides caesigalina Rum ( Bacteroides caecigallinarum ), Bacteroides cellulosilyticus , etc. may be, preferably Bacteroides vulgartus, but is not limited thereto. When the Bacteroides sp. strain of the present invention has an increased level of its presence compared to a normal control group, or a group before cancer growth, it can be predicted that a brain tumor has occurred, or a high probability of occurrence.

The "metabolite of the Bacteroides sp. strain" of the present invention is a product produced through the metabolic activity of the Bacteroides sp. strain, and preferably in the present invention, the metabolite means a short-chain fatty acid, more preferably preferably acetate or propionate, most preferably propionate.

As used herein, the term "brain tumor" refers to all tumors occurring within the cranial cavity. Depending on the location of occurrence, benign tumors may have poor prognosis like malignant tumors, and have a higher risk of recurrence than cancers occurring in other organs. These brain tumors can be divided into two types: primary brain tumors and metastatic brain tumors. In the case of primary, it originates in the brain itself, and in the case of metastasis, it means that it has metastasized to the brain from other organs. Glioblastoma multiforme, a type of brain tumor, is a malignant tumor with a very high degree of malignancy. According to the WHO standards, it is the most dangerous stage, stage 4, and even with surgery, chemotherapy, and radiation therapy, the survival rate for more than 5 years is 1%. is barely exceeding the level. On average, the survival rate of cancer patients improved by about 30%, but in the case of glioblastoma, the survival rate of the brain is significantly lower than 1% due to the nature of the organ. In the case of the brain, it is considered an immune tolerance organ by the blood brain barrier (BBB), and although the inflow and outflow of immune cells occurs under certain circumstances, there are still significant limitations in treatment using the third-generation anticancer drug, immunotherapy. exist. As such, in the case of brain tumors, since treatment is very difficult, it is very important to make early diagnosis compared to other carcinomas in order to effectively cope with them. However, despite such importance, especially in the case of glioblastoma, since only common symptoms that can be experienced in daily life such as headache or nausea appear, it is impossible to diagnose it early through the general process of recognizing and visiting the hospital by the patient himself/herself. Reality. As a representative diagnostic method for brain tumors such as glioblastoma, there is an MRI (Magnetic Resonance Imaging) imaging method. However, since such an MRI imaging method is very expensive, there is a limitation in that the barrier to entry is very high to be applied to a case where there is a low possibility of disease. Furthermore, in the case of MRI imaging, a metal contrast agent is administered into the body, and it cannot be applied if there is an allergic reaction to such a contrast agent. can

In the present invention, the "brain tumor" refers to both the primary and metastasis generated from the brain tissue or the membrane surrounding the brain, and metastatic metastasis to the brain tissue or the meninges in a region far from the skull or surrounding structures or the head. For the purposes of the present invention, the brain tumor may be a glioblastoma, but is not limited thereto.

The "glioblastoma" of the present invention is a tumor with the highest degree of malignancy observed histologically among tumors generated from glial cells of the brain, including nuclear atypical, mitotic, vascular endothelial cell proliferation, and necrosis. Malignant glioblastoma is the most common single tumor occurring in the brain, accounting for 12-15% of all brain tumors and 50-60% of gliomas. Since such glioblastoma possesses stem cell-like cancer cells and is highly resistant to treatment, the prognosis after treatment is poor, so it is very important to diagnose it early. When the present invention is used, it is possible to diagnose glioblastoma at an early stage with the ratio of the microorganism obtained based on easy-to-access intestinal microbial analysis, and to predict the progression stage of glioblastoma in an individual.

The "high-salt individual" of the present invention is an individual who consumes more than 40 mg/kg of sodium per day, and more preferably, an individual who consumes more than 55 mg/kg of sodium per day. In the method for predicting the risk of brain tumor onset provided by the present invention, a composition for brain tumor diagnosis in a high-salt individual, a kit for diagnosing a brain tumor in a high-salt individual, or a method for providing information on brain tumor diagnosis, a daily sodium 40mg/day In excess of kg, more preferably 55 mg/kg or more ingested while the onset of brain tumor is uncertain as an individual, which means an individual with a high probability of developing a disease.

As used herein, the term “biological sample” refers to any material, biological fluid, tissue or cell obtained from or derived from an individual, for example, one selected from the group consisting of intestinal tissue, intestinal cells and feces. It may be more than a species, but is not limited thereto.

In the present invention, the biological sample is most preferably feces, but if the presence of intestinal microorganisms can confirm the presence, the type is not particularly limited.

In one embodiment of the present invention comprising the steps of (a) determining whether the subject has a high salt diet; And (b) confirming the level at which the Bacteroides sp. strain, or its metabolite, exists in a biological sample isolated from a high-salt individual; provides a method for predicting the risk of developing a brain tumor in a high-salt individual comprising; The high-salt individual provides a method for predicting the risk of brain tumor onset of a high-salt individual, which is an individual who consumes more than 40 mg/kg of sodium per day, and the high-salt individual is an individual who consumes more than 55 mg/kg of sodium per day. It provides a method for predicting the risk of developing a brain tumor in an individual, wherein the Bacteroides sp. strain is Bacteroides vulgatus . It provides a method for predicting the risk of developing a brain tumor in an individual with a high salt diet, the Bacteroides genus The metabolite of the strain is propionate (propionate), which provides a method for predicting the risk of developing brain tumors in individuals with a high salt diet, wherein the biological sample is at least one selected from the group consisting of intestinal tissue, intestinal cells, and feces It provides a method for predicting the risk of developing a brain tumor in a high-salt individual, and the brain tumor is a glioblastoma.

In another embodiment of the present invention, there is provided a composition for diagnosing brain tumors in a high-salt individual comprising an agent for detecting a Bacteroides sp. strain, or a metabolite thereof, wherein the high-salt individual is sodium 40mg/day To provide a composition for diagnosing brain tumor in a high-salt individual who consumes more than kg, wherein the high-salt individual provides a composition for diagnosing brain tumor in a high-salt individual who consumes more than 55 mg/kg of sodium per day, Bacteroides sp. strain provides a composition for diagnosing brain tumors in individuals with a high salt diet, which is Bacteroides vulgatus , and the metabolite of the Bacteroides sp. strain is propionate (propionate). It provides a composition for diagnosing brain tumors in an eating individual, and the brain tumor is a glioblastoma.

The Bacteroides sp. strain, or an agent for detecting a metabolite thereof, is capable of effectively amplifying the Bacteroides sp. strain by complementary binding to a gene of the sp. strain, for example, 16S rRNA, etc., preferably , primers, probes, LNA, and may be at least one selected from the group consisting of antisense nucleotides, but is not limited thereto.

The "primer" is a fragment recognizing a desired gene sequence, and includes a pair of forward and reverse primers, but preferably, a primer pair that provides analysis results with specificity and sensitivity. High specificity can be conferred when the primer's nucleic acid sequence is a sequence that is inconsistent with a non-target sequence present in the sample, thus amplifying only the target gene sequence containing the complementary primer binding site and not causing non-specific amplification. .

The "probe" refers to a substance capable of specifically binding to a target substance to be detected in a sample, and refers to a substance capable of specifically confirming the presence of a target substance in a sample through the binding. The type of probe is not limited as a material commonly used in the art, but may be, for example, peptide nucleic acid (PNA), locked nucleic acid (LNA), peptide, polypeptide, protein, RNA or DNA, preferably It is PNA. More specifically, the probe is a biomaterial derived from or similar thereto, or manufactured in vitro, and includes, for example, enzymes, proteins, antibodies, microorganisms, animal and plant cells and organs, neurons, DNA, and It may be RNA, and DNA includes cDNA, genomic DNA, and oligonucleotides, RNA includes genomic RNA, mRNA, and oligonucleotides, and examples of proteins include antibodies, antigens, enzymes, peptides, and the like.

The "LNA (Locked nucleic acids)" refers to a nucleic acid analog comprising a 2'-O, 4'-C methylene bridge [J Weiler, J Hunziker and J Hall Gene Therapy (2006) 13, 496.502]. LNA nucleosides include general nucleic acid bases of DNA and RNA, and can form base pairs according to the Watson-Crick base pairing rule. However, due to the 'locking' of the molecule due to the methylene bridge, the LNA does not form the ideal shape in the Watson-Crick bond. When LNA is incorporated into DNA or RNA oligonucleotides, LNA can pair with complementary nucleotide chains more rapidly, increasing the stability of the double helix.

The "antisense nucleotide" means that the antisense oligomer hybridizes with a target sequence in RNA by Watson-Crick base pairing, allowing the formation of a typically mRNA and RNA:oligomeric heteroduplex within the target sequence and a sequence of nucleotide bases and sub It refers to an oligomer having an inter-unit backbone. An oligomer may have exact sequence complementarity or approximate complementarity to a target sequence.

The detection agent of the present invention is based on the 16s rRNA nucleotide sequence of the Bacteroides sp. strain, more specifically Bacteroides vulgatus , known in the field to which the present invention belongs, complementary to it A person skilled in the art can easily construct primers, probes, antisense nucleotides, and the like that can do this.

In another embodiment of the present invention, there is provided a kit for diagnosing brain tumors in individuals with high salt intake, comprising the composition for diagnosing brain tumors in individuals with high salt intake.

Since the brain tumor diagnosis kit of the present invention includes the brain tumor diagnosis composition according to the present invention, the contents related to Bacteroides spp. strain, detection agent, brain tumor, glioblastoma, primer, probe, etc. are provided to avoid excessive complexity of the specification. omit

The kit of the present invention may further include one or more other component compositions, solutions or devices suitable for the assay method.

The kit of the present invention may further include, for example, essential elements necessary for performing a reverse transcription polymerase reaction. The reverse transcription polymerase reaction kit includes a pair of primers specific for a gene encoding a marker protein. The primer pair is a nucleotide having a sequence specific to the nucleic acid sequence of the gene, and may have a length of, for example, about 7 bp to 50 bp, or about 10 bp to 30 bp. It may also include a pair of primers specific for the nucleic acid sequence of the control gene. Other reverse transcription polymerase reaction kits include test tubes or other suitable containers, reaction buffers (with varying pH and magnesium concentrations), deoxynucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNase, RNase inhibitor DEPC -Water (DEPC-water), sterile water, etc. may be further included.

The kit of the present invention may include essential elements necessary for performing a DNA chip. The DNA chip kit may include a substrate to which cDNA or oligonucleotide corresponding to a gene or fragment thereof is attached, and reagents, agents, enzymes, etc. for preparing a fluorescently-labeled probe. The substrate may also contain cDNA or oligonucleotides corresponding to control genes or fragments thereof.

In another embodiment of the present invention, (a) determining whether the subject has a high salt diet; And, (b) confirming the level of the Bacteroides sp. strain, or a metabolite thereof in a biological sample isolated from a high-salt individual; a method of providing information on brain tumor diagnosis in a high-salt individual comprising a; It provides, and the high-salt individual provides a method of providing information on brain tumor diagnosis in a high-salt individual who is an individual who consumes in excess of 40 mg/kg of sodium per day, wherein the high-salt individual consumes 55 mg/kg of sodium per day It provides a method for providing information on the diagnosis of brain tumors in individuals with high salt intake, which is an individual who consumes more than kg, wherein the Bacteroides spp. strain is Bacteroides vulgatus . Brain tumors in individuals with high salt diet It provides a method for providing information on diagnosis, and the metabolite of the Bacteroides sp. strain is propionate (propionate). It provides a method for providing information on the diagnosis of brain tumors in individuals with a high salt diet, wherein the The biological sample provides a method for providing information on the diagnosis of a brain tumor in a high-salt individual who is at least one selected from the group consisting of intestinal tissue, intestinal cells, and feces, wherein the brain tumor is a glioblastoma. To provide a method for providing information on the diagnosis of brain tumors in

The method for providing information of the present invention includes the step of detecting the level of the presence of a Bacteroides sp. strain, or a metabolite thereof, in a biological sample isolated from a target individual.

When the Bacteroidetes sp. strain of the present invention, or the level of its metabolites present is increased compared to the normal control, it can be predicted that the incidence of brain tumor is high.

In the information providing method of the present invention, the contents related to the Bacteroides sp. strain, brain tumor, glioblastoma, etc. are the same as those described in the diagnostic composition above, and are omitted to avoid excessive complexity of the specification.

In the method of predicting the risk of developing a brain tumor in the high-salt individual of the present invention, or in the method of providing information on the diagnosis of brain tumor in a high-salt individual, "confirming the level of the presence of the Bacteroides spp. strain or its metabolite" Ham is using Real-time RT-PCR, RNase protection assay (RPA), Northern blotting, Pyrosequencing, 16S rRNA gene sequencing and DNA chip. One or more methods selected from the group consisting of may be used.

In another embodiment of the present invention, sodium, and Bacteroides vulgatus provides a composition for promoting brain tumor development comprising as an active ingredient, the brain tumor is glioblastoma It provides a composition for promoting brain tumor development do.

In another embodiment of the present invention, there is provided a composition for promoting brain tumor development comprising sodium, and propionate, a metabolite of Bacteroides vulgatus , as an active ingredient, wherein the brain tumor is glioblastoma It provides a composition for promoting brain tumor development.

In another embodiment of the present invention, there is provided a method for preparing a brain tumor animal model comprising; administering sodium, and Bacteroides vulgatus to an individual other than humans, wherein the brain tumor is glioblastoma Provided is a method for preparing a human brain tumor animal model.

In another embodiment of the present invention, sodium and Bacteroides vulgatus metabolite propionate (propionate) is administered to a subject other than a human; It provides a method for preparing a brain tumor animal model comprising And, the brain tumor provides a method for producing a brain tumor animal model that is glioblastoma.

Hereinafter, the present invention will be described in detail step by step.

The present invention relates to a composition for diagnosing brain tumors in a high-salt environment using intestinal microbes, and by detecting the level of the strain, it is possible to diagnose a brain tumor early in a very easy way.

1 is a diagram showing the results of comparison of survival rates of brain tumor mice fed a high salt diet or a control diet, according to an embodiment of the present invention.
Figure 2 is a diagram showing the results of comparison of brain tumor size of brain tumor mice fed a high salt diet or a control diet, according to an embodiment of the present invention.
3 is a diagram showing the results of comparison of survival rates of brain tumor mice fed a high salt diet or a control diet when intestinal symbiotic microorganisms are removed, according to an embodiment of the present invention.
Figures 4a to 4c, according to an embodiment of the present invention, a mock object (mock), or in the brain tumor group (Family), genus (Genus), Species (Species) stage of intestinal commensal microorganisms change amount of linear discriminant analysis size (LDA score) is a diagram shown.
Figure 5 is a diagram showing the results of comparing the proportion of Bacteroides vulgatus among the intestinal symbiotic microbial community of mice with or without a high-salt diet, brain tumor, according to an embodiment of the present invention.
Figure 6 is a diagram showing the results of comparison of survival rates of brain tumor mice administered with Bacteroides vulgartus metabolite acetate (acetate), or propionate (propionate), according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited by the following examples.

Example 1. Analysis of survival rate, and cancer size in a high-salt brain tumor animal model

To investigate the relationship between high salt diet and brain tumor, mice were restricted from diet as shown in Table 1 and maintained for 4 weeks. Thereafter, 1 x 10 ⁵ GL261, a mouse-derived brain tumor cell line, was intracranially injected to induce brain tumors.

group note Control diet (CD) Feed containing 0.5% NaCl, and regular drinking water diet High-salt diet (HSD) A diet containing 4% NaCl, and a drinking water diet containing 1% NaCl

When the weight of the mouse (about 20 g) and the amount of feed the mouse consumed during the experiment period were calculated, the control group consumed an average of 7 mg/kg of sodium per day, and the high-salt group consumed an average of 55 mg/kg of sodium per day. analyzed.

The survival rate of the prepared animal model was analyzed, and the results are shown in FIG. 1 . As a result of the experiment, it was found that the survival rate decreased when the high-salt diet was compared to the control diet.

The size of the brain tumor of the animal model was determined by intracranial injection of 1 x 10 ⁵ GL261-GFP cells expressing green fluorescent protein, and then separating the brain on a specific date to obtain an image through a confocal microscope, and using Image J program to determine the size of the tumor. By measuring the short axis and the long axis, the tumor was assumed to be an ellipse and the tumor volume was calculated. The results are shown in FIG. 2 . As a result of the experiment, when the high-salt diet was performed, the tumor size was significantly increased compared to the control diet. Through this, it was found that a high-salt diet weakened the immune response to brain tumors.

Example 2. Estimation of the cause of decreased survival rate of high-salt-eating brain tumor animals

In order to examine the effect of changes in intestinal symbiotic microorganisms due to high salt diet on the anti-brain tumor immune response, an animal model was prepared by restricting the diet in the same manner as in Example 1, but all mice were treated with Ampicillin to remove intestinal symbiotic microorganisms. (500 mg/L), Gentamycin (500 mg/L), Metronidazole (500 mg/L), Neomycin sulfate (500 mg/L), and Vancomycin (250 mg/L) combination antibiotics from 2 weeks before transplantation of brain tumor cell lines For a total of 4 weeks, 200 μl per mouse was administered orally for 5 days a week.

The survival rate of the prepared animal model was analyzed, and the results are shown in FIG. 3 . As a result of the experiment, there was no significant difference in survival rate between the control group and the high salt group. Through this, it could be estimated that the decrease in the survival rate of the high-salt group in Example 1 was due to the composition of the intestinal symbionts changed by the high-salt diet.

Example 3. Analysis of changes in intestinal symbiotic microorganisms due to high salt diet

From the results of Example 2, an analysis of changes in intestinal symbiotic microorganisms was performed in order to find out which changes in the intestinal symbionts weakened the immune response to brain tumors in a high-salt environment.

To this end, in the same manner as in the animal model of Example 1, an animal model in which brain tumor cells were transplanted or not transplanted while restricting diet was prepared, and a fecal sample was obtained from the animals on the 15th day and DNA was extracted therefrom. Then, 16S ribosomal DNA sequencing was performed on the extracted DNA to analyze the composition of the intestinal symbiotic community. In order to find strains significantly different between groups in the analysis, LDA (linear discriminant analysis) effect size (LEfSe) method was used in each of the family, genus, and species stages. . The results are shown in FIG. 4 . Experimental results, Bacteroides vulgatus ( Bacteroides vulgatus ) was found to increase in a high salt diet in common. In addition, as a result of comparing the proportion of Bacteroides vulgartus in the colony of intestinal symbiotic microorganisms in the group with or without transplantation of cancer cells in the high-salt model, the Bacteroides were impossible in the high-salt diet compared to the control diet, regardless of the presence or absence of cancer. It was found that the ratio of teeth significantly increased. This is shown in FIG. 5 .

Example 4. Analysis of the effect of Bacteroides vulgartus metabolites in brain tumors

Bacteroides vulgartus is known to produce acetate and propionate of a short-chain fatty acid type, and since it was confirmed from Example 3 that Bacteroides vulgartus increased in a high salt environment, the The effect of Bacteroides vulgartus metabolites on anti-brain tumor immune response was analyzed.

To this end, an animal model in which drinking water containing 200 mM sodium propionate or 200 mM sodium acetate was fed 4 weeks before cancer cell transplantation was prepared. Considering sodium contained in sodium propionate and sodium acetate used in the experiment, drinking water containing 200 mM sodium chloride was fed as a control.

The survival rate of the prepared animal model was analyzed, and the results are shown in FIG. 6 . As a result of the experiment, the group treated with acetate had no difference in survival rate compared to the control group, but the group treated with propionate had a significantly reduced survival rate compared to the control group. Therefore, it was found that propionate attenuated the anti-brain tumor immune response.

As described above in detail a specific part of the present invention, for those of ordinary skill in the art, this specific description is only a preferred embodiment, and it is clear that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (14)

(a) determining whether the subject has a high salt diet; and,
(B) confirming the level at which Bacteroides sp. strains, or metabolites thereof, exist in a biological sample isolated from a high-salt individual; Containing, a method for predicting the risk of developing brain tumors in a high-salt individual.
The method of claim 1,
The high-salt individual is an individual who consumes more than 40 mg/kg of sodium per day, a method for predicting the risk of brain tumors in a high-salt individual.
3. The method of claim 2,
The high-salt individual is an individual who consumes more than 55 mg/kg of sodium per day, a method for predicting the risk of developing brain tumors in a high-salt individual.
The method of claim 1,
The Bacteroides sp. strain is Bacteroides vulgatus ( Bacteroides vulgatus ) The method for predicting the risk of developing brain tumors in high-salt individuals.
The method of claim 1,
The metabolite of the Bacteroides sp. strain is propionate (propionate), a method for predicting the risk of brain tumor onset in a high salt individual.
The method of claim 1,
The biological sample is one or more selected from the group consisting of intestinal tissue, intestinal cells, and feces.
The method of claim 1,
The brain tumor is a glioblastoma, a method of predicting the risk of developing a brain tumor in a high-salt individual.
Bacteroides ( Bacteroides ) Sp. strain, or a composition for diagnosing brain tumors in a high salt individual comprising an agent for detecting a metabolite thereof.
A kit for diagnosing brain tumors in a subject with a high salt diet, comprising the composition for diagnosis of claim 8.
(a) determining whether the subject has a high salt diet; and,
(B) confirming the level of the Bacteroides sp. strain, or metabolites thereof in the biological sample isolated from the high-salt individual;
Sodium, and Bacteroides vulgatus ( Bacteroides vulgatus ) A composition for promoting brain tumor development, comprising as an active ingredient.
Sodium, and Bacteroides vulgatus ( Bacteroides vulgatus ) The metabolite propionate (propionate) containing as an active ingredient, a brain tumor promotion composition.
Sodium, and Bacteroides vulgatus ( Bacteroides vulgatus ) to an individual other than humans;
Sodium, and Bacteroides vulgatus ( Bacteroides vulgatus ) administering a metabolite propionate (propionate) to an individual other than human; Containing, a method for producing a brain tumor animal model.

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